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:

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:

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:

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:

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:

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:

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:

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:

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:

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)

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: