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 #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)