- Last 7 days
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Case: patient is named case #2, male
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: Hyperammonemia (HP:0001987), oriticaciduria (HP:0003218), low plasma citrulline (HP:0003572), neonatal onset(HP:0003623), Hyperglutaminemia (HP:0003217)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: GDNA was isolated from lymphocytes. To examine the small mutations in the coding region of the OTC gene, all 10 exons and their flanking intron regions were amplified using PCR, and the nucleotide sequences of the amplified products were determined. To determine the intron 5 sequence of case 2, PCR was performed using primers OTCex5F and OTCint5R, and primers OTCint5F and OTCex6R (Table 1, Fig. 3). The amplified products were subcloned into the pT7 vector and the inserted DNA was sequenced using an automated DNA sequencer. Allopurinol test
Supplemental Data: TABLE 1, Notes:
Variant: NM_000531.6: c.540+265G>A
ClinVarID: NA
CAID: CA658658977
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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- Sep 2024
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Case: Patient #8, Female, Spanish
DiseaseAssertion: UCD/OTCD
FamilyInfo: Family history of disease
CasePresentingHPOs: Hyperammonemia (HP:0001987), Hyperglutaminemia (HP:0003217), Low plasma citrulline (HP:0003572), Oroticaciduria (HP:0003218), Childhood onset (HP:0011463)
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Patients referred for mutational study because of enzymatically proven and/or laboratory proven OTC deficiency; genomic DNA extracted using commercial kit; amplified through PCR; SSCP analysis; sequenced using ABI Prism 3100 automated sequencer
SupplementalData: Table 1
Variant: NM_000531.6: c.391_397dup (p.Ser133Ilefs*3)
ClinVarID: 597358
CAID: CA913190354
gnomAD:
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- Aug 2024
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Case: Patient Proband SS, Female, Caucasian
DiseaseAssertion: UCD/OTCD
FamilyInfo: De novo inheritance, no family history of disease
CasePresentingHPOs: Hyperammonemia (HP:0001987), oroticaciduria (HP:0003218), Childhood onset (HP:0011463)
CaseHPOFreeText:
CaseNOTHPOs: Positive allopurinol test
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA isolated from peripheral blood leukocytes or cultured skin fibroblasts. Amplification by PCR used. SSCP analysis performed. Sequencing of both free and immobilized single strands carried out by dideoxy chain termination method.
SupplementalData: Table 1: Mutations in the Ornithine Transcarbamylase Gene of 17 Females
Variant: NM_000531.6:c.77+1G>A
ClinVarID: 97313
CAID: CA224773
gnomAD:
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Case: Female Patient #1, Female, Japanese
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: Childhood onset (HP:0011463)
CaseHPOFreeText: Onset at 2 years
CaseNOTHPOs:
CaseNOTHPOFreeText: 16% OTC activity
CasePreviousTesting:
Variant: NM_000531.5:c.67C>T (p.Arg23*)
ClinVarID: 97292
CAID: CA224742
gnomAD:
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Case: Patient #38, Female, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: No family history of disease, mutation is inherited
CasePresentingHPOs: Hyperammonemia (HP:0001987), oroticaciduria (HP:0003218), vomiting (HP:0002013), coma (HP:0001259), lethargy (HP:0001254), seizures (HP:0001250), childhood onset (HP:0011463)
CaseHPOFreeText: Elevated plasma ammonia at 190 umol/L (Normal: 9-30 umol/L), Elevated urinary orotate at 202 mmol/mmol creatinine (Normal: 0-1.5 mmol/mmol creatinine)
CaseNOTHPOs:
CaseNOTHPOFreeText: Normal plasma glutamine at 13.5 umol/L (Normal: 6-30 umol/L), Normal plasma citrulline at 15.75 umol/L (Normal: 7-35 umol/L)
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
Variant: NM_000531.6:c.67C>T (p.Arg23*)
ClinVarID: 97292
CAID: CA224742
gnomAD:
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Case: Patient #4, Female, Caucasian
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: Hyperammonemia (HP:0001987),
CaseHPOFreeText: Elevated plasma ammonia concentration at 123 uM/L
CaseNOTHPOs:
CaseNOTHPOFreeText: Anxiety, plasma citrulline at 2 uM/L
CasePreviousTesting: N/A
Variant: NM_000531.5:c.67C>T (p.Arg23*)
ClinVarID: 97292
CAID: CA224742
gnomAD:
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Case: Patient #16, Male
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: Neonatal onset (HP:0003623), Hyperammonemia (HP:0001987)
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: N/A
Variant: NM_000531.6: c.77+2dupT
ClinVarID: 567293
CAID: CA891844248
gnomAD:
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Case: Patient #50, Male
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: Neonatal onset (HP:0003623), Hyperammonemia (HP:0001987)
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: N/A
Variant: NM_000531.6: c.174G>A (p.Trp58*)
ClinVarID: 97127
CAID: CA224490
gnomAD:
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Case: Patient #85, Male
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNOTHPOs: Late Onset
CaseNOTHPOFreeText: Milder phenotype
CasePreviousTesting: N/A
Variant: NM_000531.6: c.298+1G>T
ClinVarID: 97160
CAID: CA224544
gnomAD:
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Case: Patient #32, Female
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: N/A
Variant: NM_000531.6: c.140dup (p.(Asn47LysfsTer8))
ClinVarID:
CAID:
gnomAD:
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Case: Patient #7, Female
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: N/A
Variant: NM_000531.6: c.29_32del (p.Asn10fs)
ClinVarID: 97157
CAID: CA224540
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: Patient #15, Female
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
Variant: NM_000531.6: c.77+1G>A
ClinVarID: 97313
CAID: CA224773
gnomAD:
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- Jul 2024
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Case: patient #10, Male, Argentine
Disease Assertion: UCD/OTCD
Family Info: family history of the disease,
Case Presenting HPOs: Neonatal onset(HP:0003623), Hyperammonemia HP:0001987
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The OTC gene mutations were identified using PCR amplification, classical sequencing (Sanger), and multiplex ligation-dependent probe amplification.10,11 Mutations were identified by comparison with the GenBank reference sequence for human OTC (GenBank entries: NG_008471.1, NP 000522.3, NM 000531.5, NC 000023.11) Missense mutations were analyzed using different computational algorithms: CLUSTALW2 (http://www.clustal.org/clustal2/), SIFT (http://blocks.fhcrc.org/sift/SIFT.html),Polyphen2(http://genetics.bwh.harvard.edu/pph/),PoPMuSiC(http://babylone.ulb.ac.be/popmusic/), and SIFT Indel(http://siftdna.org/www/SIFT_indels2.html).
Supplemental Data: Table 1 Notes: died at 6 months and had 2 brothers that died a neonatal stage
Variant: NM_000531.6: c.540+1G>A
ClinVarID: 1458773
CAID: CA412724226
gnomAD: X-38381340-A-T
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient#5 , female, Italian
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: irritability(HP:0000737), lethargy(HP:0001254), vomiting(HP:0002013), Oriticaciduria (HP:0003218), low plasma citrulline (HP:0003572), Elevated circulating alanine aminotransferase concentration(HP:0031964), Elevated circulating aspartate aminotransferase concentration (HP:0031956), childhood onset (HP:0011463)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Total RNA was isolated from peripheral blood lymphocytes or lymphoblastoid cell lines and from frozen liver biopsy as described in Chomczynski and Sacchi (1987). For each patient two cDNA syntheses were performed: 10mg of total RNA with 800-1000 ng of oligo dT or 500ng of specific primer NR, mapping in the 3’UTR of OTC cDNA Identification of genetic lesions by amplification of the OTC mRNA, expressed in the liver tissue and intestine, from a non-specific tissue like PBL or lymphoblastoid cell lines. Some mutations, particularly those affecting splicing sites, may have a different expression in liver and PBL . In females, including manifesting carriers, this method allows the identification of deletions and gene rearrangements with certainty, but mutations, decreasing mRNA stability, are unlikely to be detected because the normal allele will constitute the majority of the RNA available for RT-PCR and will be preferentially amplified.
Supplemental Data: Case report section Notes: Hepatomegaly. This mutation, previously reported (Reish et al., 1993), has been correlated with a lethal disease form in a male patient, therefore the mild phenotype in our patient could be explained by a not completely unfavorable X-lyonization
Variant: NM_000531.6: c.928G>T(p.Glu310*)
ClinVarID: 97361
CAID: CA224838
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: 24 yo Laotse patient , female
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs:Hyperammonemia(HP:0001987), Adult onset (HP:0003581), Elevated circulating alanine aminotransferase concentration(HP:0031964), Elevated circulating aspartate aminotransferase concentration(HP:0031956), oriticaciduria(HP:0003218), Aminoaciduria(HP:0003355, Prolonged prothrombin time(HP:0008151), Cerebral edema(HP:0002181),
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: " Genomic DNA from the patient was isolated from cultivated fibroblasts. Nine pairs of primers were designed from the published sequence of the OTC gene6,7 to allow amplification of all 10 exons including adjacent intron sequences. Single-strand conformational polymorphism analysis of the polymerase chain reaction–amplified individual exon 8 yielded an unusual migration pattern of exon 9
Supplemental Data: Case report section Notes: Patient had a pregnancy 2 years prior and lost the baby. In this case report, She was a 14weeks pregnant(2nd pregnancy) 24yo . She died during this of severe hyperammonemia 5 days after being administered amino acids through parenteral nutrition. She developed signs of encephalopathy stage 4 with maximal dilated unresponsive pupils, brisk oculocephalic reflex, and severe hyperventilation, requiring mechanical ventilation. MRI revealed revealed diffuse cortical edema with loss of white to gray matter distinction. Increased excretion of Gly, Gln, Ser, Thr, and Lys was found in her urine. Treatment with benzoate was started but didn't save the patient.
Variant: NM_000531.6: c.892_893del(p.Trp298Aspfs*15)
ClinVarID: 97348
CAID: CA224820
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #11, female, 35yo, slovenian
Disease Assertion: UCD/OTCD
Family Info: family history of the disease,
Case Presenting HPOs: Adult onset(HP:0003581), hyperammonemia(HP:0001987), protein avoidance (HP:0002038)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Sequencing was performed at a 3rd-party sequencing center using a standardized seq of procedures following PCR-free WGS library preparation protocol Illumina TrueSeq DNA Nano and sequenced on Illumina NovaSeq 6000 platform with a mean autosomal depth greater than 30×. Variants were interpreted by a medical doctor specialized in the NGS sequencing data analysis and those classified as likely pathogenic or pathogenic according to the ACMG/AMP standards and guidelines were considered for reporting, while variants of uncertain clinical significance, were not considered. Likely pathogenic and pathogenic variants were further evaluated by the referring clinical geneticist and were considered and reported if they were classified as both a likely diagnostic finding and if they were compatible with the clinical presentation of referral.
Supplemental Data: Table 4 and section 3.1(Case description) Notes:
Variant: NM_000531.6: c.540+265G>A
ClinVarID: 449382
CAID: CA658658977
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #113, Male
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: Neonatal onset(HP:0003623), Hyperammonemia HP:0001987
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: GDNA from blood, cultured skin fibroblasts, liver from patients suspected for otc deficiency was used to amplify all 10 exons and exon/intron boundaries using primers listed in Table 1. The amplified DNA fragments were then screened by single-strand conformational polymorphism (SSCP) and the abnormally migrating DNA fragments were sequenced directly from PCR products (w/o subcloning) to identify the mutation. The amino acid residue substitution created by the mutation is examined using an alignment of 26 OTCase sequences from 23 species.
Supplemental Data: Table 4 Notes:
Variant: NM_000531.6: c.867+1G>A
ClinVarID: 97342
CAID: CA224813
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #20, Male
Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: Hyperammonemia (HP:0001987), oriticaciduria (HP:0003218), low plasma citrulline (HP:0003572), neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Genomic DNA was isolated using PUREGENE blood kit from peripheral leukocytes of patients and related family members with informed consents. Amplification by PCR of all 10 exons of the OTC gene was performed using nine pairs of primers designed to span all exons and their adjacent intronic regions. PCR products were subsequently sequenced using ABI3100 Genetic analyzer with BigDye termination ver.3.0.To analyze the activity of OTC protein expressed in the COS-7, high-pressure liquid chromatographic (HPLC) analysis was performed with a Water system, consisting of a model 510 pump and a UV-visible 420 detector.
Supplemental Data: Table 1 Notes:
Variant: NM_000531.6: c.796_805del(p.Ile265AspfsX20)
ClinVarID: NA
CAID: CA2695233326
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #1, female Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: Hyperammonemia (HP:0001987), Juvenile onset (HP:0003621)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "DNA samples were obtained from either peripheral white blood cells or liver biopsies of probands. Patient 1 total liver RNAs were extracted by the acid-phenol-guanidium method and reverse-transcribed in cDNA by hexanucleotide priming using Superscript 11' (Life Technologies, Cergy-Pantoia, France). First strand cDNA was further PCR-amplified using forward and reverse primers specificons 7 and 9 of the OTC gene, respectively. Sequence comparisons were conducted using the FASTA option of the BISANCE package. Secondary protein conformational changes induced by sequence mutations were predicted using the algorithms of the BISANCE package. Nucleotidic changes potentially altering splice sites were studied using the Senapathy's algorithm from the BISANCE package."
Supplemental Data: TABLE 1, Notes:
Variant: NM_000531.6: c.731_739del(p.Leu244Profs)
ClinVarID: 97307
CAID: CA224765
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #273, Male
Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: Supplemental table file Notes:
Variant: NM_000531.6: c.818del (p.Glu273Glyfs*16)
ClinVarID: 97338
CAID: CA224807
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient MW
Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: NA
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: NA Notes: mutation might cause exon 8 kipping durring splicing.
Variant: NM_000531.6: c.718-2A>G
ClinVarID: 97303
CAID: CA224761
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #5, male, German Disease Assertion: UCD/OTCD
Family Info: Family history of the disease, Variant found in mother of the patient
Case Presenting HPOs: infantile onset (HP:0003593), oritic aciduria(HP:0003218), hyperammonemia(HP:0001987), hyperglutaminemia(HP:0003217), low plasma citrulline (HP:0003572)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Liver tissues were used to extract RNA that was later used to synthesize cDNA. The products were compared to healthy controls in order to detect variants. gDNA, in order to determine the size of deletions in patient 3 and 4 , a set of intronic primers presumably flanking the deletions was used and specific primers allowed sequencing of exactly those critical regions(sequencing on paper). To estimate the relevance of the identified intronic variants in terms of their capability to induce splicing, we used a score developed by Shapiro and Senapathy. This splice score offers information about the usage of a certain splice site
Supplemental Data: TABLE 1, Notes: died at 11 months, was given medication and low protein diet and was asymptomatic during that time. Died from sever cerebral edema.
Variant: NM_000531.6: c.1005+1091C>G
ClinVarID: N/A
CAID: CA2695233334
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #1, male, turkish
Disease Assertion: UCD/OTCD
Family Info: Family history of the disease, Variant found in mother of the patient
Case Presenting HPOs: infantile onset (HP:0003593), coma(HP:0001259), episodic hyperammonemia(HP:0001951), oriticaciduria(HP:0003218)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Liver tissues were used to extract RNA that was later used to synthesize cDNA. The products were compared to healthy controls in order to detect variants. gDNA, in order to determine the size of deletions in patient 3 and 4 , a set of intronic primers presumably flanking the deletions was used and specific primers allowed sequencing of exactly those critical regions(sequencing on paper). To estimate the relevance of the identified intronic variants in terms of their capability to induce splicing, we used a score developed by Shapiro and Senapathy. This splice score offers information about the usage of a certain splice site
Supplemental Data: TABLE 1, Notes: very mild movement disorder, the diagnosis was prenatal so measures were taken from birth,. 2 biopsies were performed and the revealed respectively a 30% and 50 % decrease on OTC activity.
Variant: NM_000531.6: c.867+1126A>G
ClinVarID: 571311
CAID: CA891843643
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #2, male, Saudi Arabian
Disease Assertion: UCD/OTCD
Family Info: Family history of the disease, Variant found in mother of the patient, Brother died of hyperammonemic crisis
Case Presenting HPOs: intellectual disability (HP:0001249), Neonatal onset (HP:0003623), seizure(HP:0001250), episodic hyperammonemia(HP:0001951), intellectual disability (HP:0001249)
Case HPO FreeText: hyperammonemic encephalopathy
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Liver tissues were used to extract RNA that was later used to synthesize cDNA. The products were compared to healthy controls in order to detect variants. gDNA, in order to determine the size of deletions in patient 3 and 4 , a set of intronic primers presumably flanking the deletions was used and specific primers allowed sequencing of exactly those critical regions(sequencing on paper). To estimate the relevance of the identified intronic variants in terms of their capability to induce splicing, we used a score developed by Shapiro and Senapathy. This splice score offers information about the usage of a certain splice site
Supplemental Data: TABLE 1, Patient was severely mentally retarded after the age of 2. Low OTC activity
Variant: NM_000531.6: c.540+265G>A(p.Gln180_Glu181insX4)
ClinVarID: 449382
CAID: CA658658977
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient #ID, female Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: NA
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: TABLE 1, Notes: NA
Variant: NM_000531.6: c.665del(p.(Gly222ValfsTer8)
ClinVarID: 97289
CAID: CA224738
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient #ID, female Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: NA
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: TABLE 1, Notes: NA
Variant: NM_000531.6: c.663+2T>C
ClinVarID: 97285
CAID: CA224732
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient #ID, male Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: NA
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: TABLE 1, Notes: NA
Variant: NM_000531.6: c.663+1G>A
ClinVarID: 97283
CAID: CA224730
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient #ID, female Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: NA
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: TABLE 1, Notes: NA
Variant: NM_000531.6: c.77+1G>T
ClinVarID: 97314
CAID: CA224774
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient ID#, 36yo donor , female
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: adult onset (HP:0003581), oriticaciduria (HP:0003218), irritability (HP:0000737), protein avoidance
Case HPO FreeText: hyperammonemic encephalopathy
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: N/A
Supplemental Data: TABLE 1, She is vegeterian. The symptoms of OTCD started showing after the patient donated 60% of liver to her sibling. the information reported in this is the biochemical results during hyperammonemic episode following the transplantation. the patient became irritable and confused, and her level of consciousness deteriorated markedly. After hemodialysis the patient recovered.
Variant: NM_000531.6: c.429T>A(p.Tyr143*)
ClinVarID: 1072591
CAID: CA412723166
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient ID#, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: GDNA was extracted from blood or liver tissues using salt and ethanol precipitation. multiplex amplification for exons 1, 5 and 9 to screen male patients with large deletions. Band intensities were measured using a molecular dynamics phosphoimager.
Supplemental Data: TABLE 2
Variant: NM_000531.6: c.541-2A>G
ClinVarID: 97243
CAID: CA224675
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient ID#, male
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: GDNA was extracted from blood or liver tissues using salt and ethanol precipitation. multiplex amplification for exons 1, 5 and 9 to screen male patients with large deletions. Band intensities were measured using a molecular dynamics phosphoimager.
Supplemental Data: TABLE 2,
Variant: NM_000531.6: c.437C>G(p.Ser146*)
ClinVarID: 97201
CAID: CA224606
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #573, male
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs:hyperammonemia (HP:0001987), Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: GDNA extracted from blood leukocytes using the proteinase K/phenol extraction procedure on a model 340 A nucleic acid extractor (Applied Biosystems). 5mg samples of DNA were digested with BamHI, MspI, or TaqI restriction endonuclease, electrophoresed through 1 % agarose gels, and transferred to a nylon membrane by standard procedures. The blots were then hybridized with a radiolabeled full-length cDNA probe for human OTC.
Supplemental Data: TABLE 3,
Variant: NM_000531.6: c.67C>T(p.Arg23*)
ClinVarID:97292
CAID: CA224742
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient SM, male
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: Hyperammonemia (HP:0001987), Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: GDNA extracted from blood leukocytes using the proteinase K/phenol extraction procedure on a model 340 A nucleic acid extractor (Applied Biosystems). 5mg samples of DNA were digested with BamHI, MspI, or TaqI restriction endonuclease, electrophoresed through 1 % agarose gels, and transferred to a nylon membrane by standard procedures. The blots were then hybridized with a radiolabeled full-length cDNA probe for human OTC.
Supplemental Data: TABLE 3,
Variant: NM_000531.6: c.274C>T(p.Arg92*)
ClinVarID:97151
CAID: CA224530
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
-
drive.google.com drive.google.com
-
Case: patient from family 1, male
Disease Assertion: UCD/OTCD
Family Info: Family history of the disease
Case Presenting HPOs: coma(HP:0001259), lethargy(HP:0001254), hyperammonemia (HP:0001987), Neonatal Onset HP:0003623
Case HPO FreeText: Poor feeding, poor spirit
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Genomic DNA was extracted using the QIAamp DNA Blood Midi Kit (Qiagen, Duesseldorf, Germany). Quality control assessment of DNA samples was performed using the NanoDrop 2000 ultra-microvolume nucleic acid and protein spectrophotometer (Thermo, Waltham, MA, USA). The purity of DNA was required to be between 1.8 and 2.0.
Supplemental Data: TABLE 1, admitted to neonatal department because of poor feeding, poor spirit, coma, and lethargy. The maternal grandmother of the proband in this family had given birth to 3 boys and 2 girls. Two boys died within 1 month after birth
Variant: NM_000531.6: c.867+1G>C
ClinVarID:N/A
CAID: CA412723994
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
-
drive.google.com drive.google.com
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Case: patient #5, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.53del (p.His18Profs*20)
ClinVarID: 97239
CAID: CA224671
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #85, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.449_451del(p.Leu151Trpfs*36)
ClinVarID: N/A
CAID: CA2759533410
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #154, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.664-1G>A
ClinVarID: 97288
CAID: CA224811
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #188, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.835C>T(p.Gln279*)
ClinVarID: 97341
CAID: CA224811
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #213, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.962C>A(p.Ser321*)
ClinVarID: 97373
CAID: CA224859
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #220, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: Table 1
Variant: NM_000531.6: c.1005+2T>C
ClinVarID: 97090
CAID: CA224431
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
Tags
- CAID: CA224671
- CAID: CA2759533410
- ClinVar: 97239
- c.1005+2T>C
- Mutation: Splicing LOF
- PMID:11793468
- ClinVar: 97373
- CAID: CA224859
- ClinVar: 97090
- c.53delA
- CAID: CA224737
- ClinVar: 97288
- c.962C>A
- ClinVar: 97341
- CAID: CA224431
- c.664-1G>A
- CAID: CA224811
- Mutation: Nonsense
- Mutation: Frameshift
- Gene: OTC
- c.835C>T
- c.449_451delC
Annotators
URL
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-
drive.google.com drive.google.com
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Case: patient #335, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: No specific functional tests indicated
Supplemental Data: In supplemental data files
Variant: NM_000531.6: c.861_862insAC (p.Met288Thrfs*2)
ClinVarID: N/A
CAID: CA2759522140
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #303, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: No specific functional tests indicated
Supplemental Data: In supplemental data files
Variant: NM_000531.6: c.766G>T(p.256Gly*)
ClinVarID: 870326
CAID: CA412722685
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #212, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: No specific functional tests indicated
Supplemental Data: In supplemental data files
Variant: NM_000531.6:c.561delA(p.Gly188Valfs*18)
ClinVarID: N/A
CAID: CA2499307429
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #198, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: No specific functional tests indicated
Supplemental Data: In supplemental data files
Variant: NM_000531.6:c.538C>T(p.Gln180*)
ClinVarID: N/A
CAID: CA412724187
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
-
drive.google.com drive.google.com
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Case: patient #16, female, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The severity of missense mutations was assessed using conservation and solvent accessible area of the replaced amino acid, calculated destabilization of mutant proteins and their SIFT and PolyPhen2 scores
Supplemental Data: Kido_et_al_2022_fgene_Data Sheet 2
Variant: NM_000531.6:c.77+1G>T
ClinVarID: 97314
CAID: CA224774
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
-
drive.google.com drive.google.com
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Case: patient #55, male, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Seizure (HP:0001250), Hyperammonemia (HP:0001987), Intellectual disability (HP:0001249)
Case HPO FreeText: abnormal brain MRI and brain waves, acute liver failure, corneal opacity
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1
Variant: NM_000531.6:c.c.929_931del(p.Glu310Valfs*45)
ClinVarID: 858012
CAID: CA916083888
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #56, female, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: ,Hyperammonemia (HP:0001987)
Case HPO FreeText: N/A
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1, patient had a liver transplant at 12yo.
Variant: NM_000531.6:c.940G>T(p.Glu314*)
ClinVarID: N/A
CAID: CA412726302
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #52, female, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: ,Hyperammonemia (HP:0001987)
Case HPO FreeText: N/A
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1
Variant: NM_000531.6:c.894G>A(p.Trp298*)
ClinVarID: N/A
CAID: CA412725724
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #51, male, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: neonatal(HP:0003623), intellectual disability (HP:0001249), seizure (HP:0001250),Hyperammonemia (HP:0001987)
Case HPO FreeText: Hypertonus, Autism, Acute liver failure. very high blood ammonia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1
Variant: NM_000531.6:c.867+1G>C
ClinVarID: N/A
CAID: CA412723994
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: patient #50, male, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Seizure HP:0001250, hyperammonemia HP: 0001987
Case HPO FreeText: Hepatomegaly, Abnormal brain MRI and brain waves, Acute liver failure, Corneal opacity
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1
Variant: NM_000531.6:c.834_840del(p.Gln279Serfs*8)
ClinVarID: N/A
CAID: CA2695233329
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
-
drive.google.com drive.google.com
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Case: no patient ID, Female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0001951, HP: 0001987
Case HPO FreeText: episodic hyperammonemia, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.
Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.
Variant: NM_000531.6:c.1052delA(p.Lys351Serfs*44)
ClinVarID: 915468
CAID: CA1139667400
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: no patient ID, Female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0003623, HP: 0001987
Case HPO FreeText: Neonatal onset, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.
Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.
Variant: NM_000531.6:c.766G>T(p.Gly256*)
ClinVarID: 870326
CAID: CA412722685
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: no patient ID, Female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0001951, HP: 0001987
Case HPO FreeText: episodic hyperammonemia, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.
Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.
Variant: NM_000531.6:c.568dupA(p.Thr190Asnfs*35)
ClinVarID: 870328
CAID: CA916083887
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: no patient ID, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0003623, HP: 0001987
Case HPO FreeText: Neonatal onset, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.
Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.
Variant: NM_000531.6:c.217-2A>G(IVS2)
ClinVarID: 915470
CAID: CA412716751
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
-
drive.google.com drive.google.com
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Case: Patient #27, male, Korean
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0003593, HP:0003218, HP: 0001987
Case HPO FreeText: Infantile onset, oroticaciduria, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.929_931del(p.Glu310Valfs*45)
ClinVarID: N/A
CAID: CA916083888
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: Patient #37, female, Korean
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0011463, HP:0003218, HP: 0001987
Case HPO FreeText: Childhood onset, oroticaciduria, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.1043delA(p.Gln348Argfs*47)
ClinVarID: N/A
CAID: CA2695233335
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: Patient #35, female, Korean
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0011463, HP:0003218, HP: 0001987
Case HPO FreeText: childhood onset, oroticaciduria, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, This is a large deletion. The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.853C>T(p.Gln285*)
ClinVarID: N/A
CAID: CA412723777
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: Patient #34, female, Korean
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0011463, HP:0003218, HP: 0001987
Case HPO FreeText: childhood onset, oroticaciduria, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, This is a manifesting heterozygote. Serum Gln+Glu was considered elevated. The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.717+1G>T(IVS7+1G>T)
ClinVarID: 97298
CAID: CA224753
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
-
Case: Patient #30, female, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: HP:0011463, HP:0003218
CaseHPOFreeText: childhood onset, oroticaciduria,
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, Serum Gln+Glu was considered elevated, the minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.491C>G(p.Ser164*)
ClinVarID: 97220
CAID: CA224642
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #6, male, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218
CaseHPOFreeText: Neonatal onset, hyperammonemia, oroticaciduria,
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, the minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.461_471del(p.Glu154Alafs*18)
ClinVarID: N/A
CAID:CA2695233305
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
Tags
- c.929_931del
- ClinVar: 97220
- CAID: CA224642
- CAID: CA224753
- c.1043delA
- c.461_471del
- CAID: CA916083888
- Mutation: Splicing LOF
- c.853C>T
- c.717+1G>T
- CAID: CA2695233305
- PMID: 23278509
- CAID:CA2695233335
- CAID: CA412723777
- Mutation: Nonsense
- Mutation: Frameshift
- Gene: OTC
- ClinVar: 97298
- c.491C>G
Annotators
URL
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drive.google.com drive.google.com
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Case: Patient #15, male, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003572
CaseHPOFreeText: Neonatal onset, hyperammonemia, oroticaciduria, low plasma citrulline
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, mother is a carrier, no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6:c.796_805del(p.Ile265_Gly268delinsAspfs*19)
ClinVarID: N/A
CAID:CA2695233326
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #45, female, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: variant in mother (father not tested) and brother
CasePresentingHPOs: HP:0003593, HP:0001987, HP:0003218
CaseHPOFreeText: infantile onset, hyperammonemia, oroticaciduria
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, mother is a carrier, the mutation was also found in patient 13(her brother), no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6c.664_667delinsAC(p.Gly222Thrfs*2)
ClinVarID: N/A
CAID:CA2695233319
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #42, female, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218
CaseHPOFreeText: Childhood onset, hyperammonemia, oroticaciduria
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6:c.958C>T(p.Arg320*)
ClinVarID: 97371
CAID:CA285809
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #44, female, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: variant in mother (father not tested)
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003217
CaseHPOFreeText: Childhood onset, hyperammonemia, oroticaciduria, hyperglutaminemia
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, mother is a carrier, no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6:c.799_800insA (p.Ser267Lysfs*26)
ClinVarID: N/A
CAID:CA2695233327
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: Patient #30, male, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: no family history of the disease
CasePresentingHPOs: HP:0003593, HP:0001987, HP:0003218
CaseHPOFreeText: infantile onset, hyperammonemia, oroticaciduria
CaseNOTHPOs:
CaseNOTHPOFreeText: No neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate)
Variant: NM_000531.6:c.929_931del(p.Glu310Valfs*45)
ClinVarID: 858012
CAID:CA916083888
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #61, female, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo:
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003572
CaseHPOFreeText: childhood onset, hyperammonemia, oroticaciduria, low plasma citrulline
CaseNOTHPOs:
CaseNOTHPOFreeText: neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate)
Variant: NM_000531.6:c.868-1G>C
ClinVarID: N/A
CAID:CA412725475
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #52, female, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: family history of the disease, variant in probands mother and father
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003572
CaseHPOFreeText: childhood onset,, hyperammonemia, oroticaciduria, low plasma citrulline
CaseNOTHPOs:
CaseNOTHPOFreeText: neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, inherited mutation, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate), low protein diet treatment, and continuous veno venous hemodialfiltration
Variant: NM_000531.6:c.703C>T
ClinVarID: N/A
CAID: CA412721652
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #20, male, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo:
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218
CaseHPOFreeText: childhood onset, hyperammonemia, oroticaciduria
CaseNOTHPOs:
CaseNOTHPOFreeText: No neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, drug treatment (L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate), deceased
Variant: NM_000531.6:c.794G>A(p.Trp265*)
ClinVarID: N/A
CAID:CA412722994
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #60, female, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: family history of the disease
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003572
CaseHPOFreeText: childhood onset,, hyperammonemia, oroticaciduria, low plasma citrulline
CaseNOTHPOs:
CaseNOTHPOFreeText: neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, inherited mutation, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate), low protein diet treatment, and continuous veno venous hemodialfiltration
Variant: NM_000531.6:c.718-1G>A
ClinVarID: N/A
CAID: CA412722112
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #58, female, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: variant pin proband's mother and father CasePresentingHPOs: HP:0003593, HP:0002038, HP:0001987, HP:0003218, HP:0003572
CaseHPOFreeText: infantile onset , protein avoidance, hyperammonemia, oroticaciduria, low plasma citrulline
CaseNOTHPOs: N/A
CaseNOTHPOFreeText: neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purifed and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplifcation analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, low protein diet treatment and drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate), neurological damage
Variant: NM_000531.6:c.540+265G>A
ClinVarID: 449382
CAID: CA658658977
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #3, male, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: Family history of the disease, variant in probands mother and father
CasePresentingHPOs: HP:0003623, HP:0001987, HP:0003218
CaseHPOFreeText: neonatal, hyperammonemia , oroticaciduria
CaseNOTHPOs: N/A
CaseNOTHPOFreeText: No neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, no therapy received, mutation inherited, family history, deceased
Variant: NM_000531.6:c.579G>A
ClinVarID: N/A
CAID: CA412725369
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #59, female, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: variant in proband's mother and father
CasePresentingHPOs: HP:0003621, HP:0001987, HP:0003218, HP:0003217
CaseHPOFreeText:juvenile onset, hyperammonemia , oroticaciduria, hyperglutaminemia
CaseNOTHPOs: N/A
CaseNOTHPOFreeText: No neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate)
Variant: NM_000531.6:c.664-1G>A
ClinVarID: 97288
CAID: CA224737
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
Tags
- c.929_931del
- c.868-1G>C
- PMID: 33272297
- CAID: CA412725475
- CAID: CA412725369
- CAID: CA916083888
- Mutation: Splicing LOF
- c.794G>A
- CAID: CA224737
- c.579G>A
- c.718-1G>A
- CAID: CA658658977
- c.664-1G>A
- Mutation: Nonsense
- cDNA: c.540+265G>A
- Mutation: Frameshift
- CAID:CA412721652
- Gene: OTC
- ClinVar: 858012
- c.703C>T
- CAID: CA412722994
- CAID:CA412722112
- ClinVar:97288
Annotators
URL
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