Case: patient #11, female, 35yo, slovenian

Disease Assertion: UCD/OTCD

Family Info: family history of the disease,

Case Presenting HPOs: Adult onset(HP:0003581), hyperammonemia(HP:0001987), protein avoidance (HP:0002038)

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: Sequencing was performed at a 3rd-party sequencing center using a standardized seq of procedures following PCR-free WGS library preparation protocol Illumina TrueSeq DNA Nano and sequenced on Illumina NovaSeq 6000 platform with a mean autosomal depth greater than 30×. Variants were interpreted by a medical doctor specialized in the NGS sequencing data analysis and those classified as likely pathogenic or pathogenic according to the ACMG/AMP standards and guidelines were considered for reporting, while variants of uncertain clinical significance, were not considered. Likely pathogenic and pathogenic variants were further evaluated by the referring clinical geneticist and were considered and reported if they were classified as both a likely diagnostic finding and if they were compatible with the clinical presentation of referral.

Supplemental Data: Table 4 and section 3.1(Case description) Notes:

Variant: NM_000531.6: c.540+265G>A

ClinVarID: 449382

CAID: CA658658977

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

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)