19 Matching Annotations
  1. Jul 2024
    1. 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)

    1. 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)

    2. 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)

    1. 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)

    1. 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)

    2. 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)

    1. 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)

    2. 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)

    1. 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)

    2. 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)

    1. 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)

    1. 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)

    2. 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)

    1. 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)

    1. 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)

    2. 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)

    3. 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)

  2. May 2022
    1. DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1

      GeneName: DICER1 PMCID: PMC7859642 HGNCID: Unavailable Inheritance Pattern: Autosomal dominant. Disease Entity: Familial pleuropulmonary blastoma (PPB), cervix embryonal rhabdomyosarcoma, multinodular goiter, nasal chondromesenchymal hemartoma, Ciliary body medulloepithelioma, Sertoli-Leydig Cell Tumor (SLCT), differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, cystic nephroma, Wilm's tumor and sarcomas of different sites including, amongst others, the uterine cervix, kidney and brain. Mutation: Germline Zygosity: Heterozygose Variant: No ClinVarID present. Family Information: No family outline Case: No specified information of patients included. CasePresentingHPO's: n/a CasePrevious Testing: n/a gnomAD: n/a Mutation Type: nonsense, frameshift, or splice affected.

  3. Apr 2022
    1. DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene.

      Gene Name: DICER1 PMID:33552988 HGNCID: Unavailable Inheritance Pattern:Autosomal Dominant Disease Entity: familial pleuropulmonary blastoma (PPB),cystic nephroma, ovarian Sertoli-Leydig cell tumor (SLCT), multinodular goiter, cervix embryonal rhabdomyosarcoma, Wilms’ tumor, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, and sarcomas of different sites. Mutation: Nonsense, Frameshift<br /> Zygosity: Heterosygosity Variant:No ClinVar ID present Family Information:no diseases mentioned in family Case: no specified case in this article gnomAD: n/a Mutation type: Nonsense. frameshift