39 Matching Annotations
  1. Last 7 days
    1. 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)

    2. 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)

    3. 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)

    1. 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)

    2. 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)

  2. Jul 2024
    1. 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)

    1. 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)

    1. 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)

    1. 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)

    1. 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)

    1. 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)

    1. 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)

    1. 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)

    1. 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)

    2. 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)

    3. 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)

    4. 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)

  3. Jul 2019
  4. Oct 2018
  5. Sep 2018
  6. Jun 2018
  7. May 2018
  8. Mar 2018
  9. Feb 2018
  10. Jan 2018
  11. Nov 2017
  12. Oct 2017
  13. Sep 2017