| Title: |
A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
| Authors: |
Runjun D. Kumar; Lindsay C. Burrage; Jan Bartos; Saima Ali; Eric Schmitt; Sandesh C.S. Nagamani; Cynthia LeMons |
| Source: |
Molecular Genetics and Metabolism Reports, Vol 26, Iss , Pp 100706- (2021) |
| Publisher Information: |
Elsevier |
| Publication Year: |
2021 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Urea cycle disorder; Genetic testing; Intronic variant; Ornithine transcarbamylase deficiency; OTC c.540+265G>A; Medicine (General); R5-920; Biology (General); QH301-705.5 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S221442692030152X; https://doaj.org/toc/2214-4269; https://doaj.org/article/b0d253dea5db4d75ab6cef3563b339b2 |
| DOI: |
10.1016/j.ymgmr.2020.100706 |
| Availability: |
https://doi.org/10.1016/j.ymgmr.2020.100706; https://doaj.org/article/b0d253dea5db4d75ab6cef3563b339b2 |
| Accession Number: |
edsbas.BCFD7CF2 |
| Database: |
BASE |