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A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing.

ABSTRACT: Pathogenic variants in non-coding regions of genes encoding enzymes or transporters of the urea cycle can lead to urea cycle disorders (UCDs). However, not all commercially available testing platforms interrogate these regions. Here, we used a gene panel based on massively parallel sequencing (MPS) in 10 individuals with clinical or pedigree-based evidence of a proximal UCD but without a molecular confirmation of the diagnosis. We identified causal variant(s) in 5 of 10 individuals, including in 3 of 7 individuals in whom prior molecular testing was unrevealing. We show that a deep-intronic pathogenic variant in OTC, c.540+265G>A, is an important cause of ornithine transcarbamylase (OTC) deficiency.

SUBMITTER: Kumar RD

PROVIDER: S-EPMC7809430 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing.

Kumar Runjun D RD Burrage Lindsay C LC Bartos Jan J Ali Saima S Schmitt Eric E Nagamani Sandesh C S SCS LeMons Cynthia C

Molecular genetics and metabolism reports 20210108

Pathogenic variants in non-coding regions of genes encoding enzymes or transporters of the urea cycle can lead to urea cycle disorders (UCDs). However, not all commercially available testing platforms interrogate these regions. Here, we used a gene panel based on massively parallel sequencing (MPS) in 10 individuals with clinical or pedigree-based evidence of a proximal UCD but without a molecular confirmation of the diagnosis. We identified causal variant(s) in 5 of 10 individuals, including in ...[more]

PMID: 33489762

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