20 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.665del(p.(Gly222ValfsTer8)

      ClinVarID: 97289

      CAID: CA224738

      gnomAD:

      Gene Name: OTC (ornithine transcarbamylase)

  2. Jul 2024
    1. Case: patient #8, female, Malaysian

      Disease Assertion: UCD/OTCD

      Family Info: Family history of the disease

      Case Presenting HPOs: Failure to thrive (HP:0001508), Seizure (HP:0001250), hyperammonemia (HP:0001987), Infantile onset (HP:0003593)

      Case HPO FreeText: hypotonia, acute encephalopathy, and respiratory distress following febrile illness.

      Case NOT HPOs:

      Case NOT HPO Free Text:

      Case Previous Testing: gDNA was isolated from peripheral blood leukocytes using a QIAamp DNA blood kit. PCR was used to amplify all 10 exons of the OTC gene using 11 pairs of synthetic oligonucleotide primers, which were tagged with a universal M13 primer. Bidirectional sequencing was conducted with Big Dye Terminator version 3.1 cycle-sequencing chemistries on a 4-channel capillary ABI 3130-Avant Genetic Analyzer. DNA sequences were aligned and compared with cDNA sequences using SeqScape Sofware version 2.5

      Supplemental Data: TABLE 1, patient died. max plasma ammonia recorded was 560 umol/L. Treatment included: Stopping protein intake, Phenytoin, Mechanic ventilation, and parenteral fluid and nutrition. Multiple neonatal death amongst maternal male siblings

      Variant: NM_000531.6: c.813_814delAGinsC(p.Glu271Aspfs*28)

      ClinVarID:N/A

      CAID: CA2695233328

      gnomAD:

      Gene Name: OTC (ornithine transcarbamylase)

    1. 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)

    2. 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)

    3. 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)

    1. 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)

    2. 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)

    1. 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)

    2. 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)

    1. 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)

    2. 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)

    1. 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)

    2. 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)

    3. 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)

    1. 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)

    2. 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)

    3. 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)

    1. 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)

  3. 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.

  4. 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