Kumar Runjun D, Burrage Lindsay C, Bartos Jan, Ali Saima, Schmitt Eric, Nagamani Sandesh C S, LeMons Cynthia
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Texas Children's Hospital, Houston, TX, USA.
Mol Genet Metab Rep. 2021 Jan 8;26:100706. doi: 10.1016/j.ymgmr.2020.100706. eCollection 2021 Mar.
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 , c.540+265G>A, is an important cause of ornithine transcarbamylase (OTC) deficiency.
编码尿素循环中酶或转运蛋白的基因非编码区的致病变异可导致尿素循环障碍（UCDs）。然而，并非所有市售检测平台都能检测这些区域。在此，我们对10名有近端UCD临床证据或基于家系证据但未得到分子诊断确认的个体，使用了基于大规模平行测序（MPS）的基因检测板。我们在10名个体中的5名中鉴定出了致病变异，包括在7名先前分子检测未发现问题的个体中的3名。我们发现，位于c.540+265G>A的一个内含子深处的致病变异是鸟氨酸转氨甲酰酶（OTC）缺乏症的一个重要病因。
