A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency.

ABSTRACT: Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder characterised by reduced or absent OTC enzyme activity, resulting in the accumulation of neurotoxic ammonia. Approximately 80%-90% of the causative variants are identified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA) of the OTC gene. A 23-year-old male with biochemical evidence of OTCD was referred for molecular analysis. Initial Sanger sequencing yielded no pathogenic variants. MLPA testing raised suspicion of a mosaic deletion of exon 1; however, high-resolution microarray did not identify a copy number variant on the X chromosome. Sequencing over the suspected breakpoint detected a hemizygous likely pathogenic promoter variant, c.-106C > A, which was located within t

SUBMITTER: Hertzog A 

PROVIDER: S-EPMC9259394 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature