靶向下一代测序在一组不明原因的线粒体功能障碍的儿科和成年患者中鉴定出新型致病性变异体，并提供分子诊断。

Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction.

机构信息

Research & Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, Porto, Portugal; Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, Porto, Portugal.

Research & Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, Porto, Portugal.

出版信息

Mitochondrion. 2019 Jul;47:309-317. doi: 10.1016/j.mito.2019.02.006. Epub 2019 Mar 1.

DOI:10.1016/j.mito.2019.02.006

PMID:30831263

Abstract

Mitochondrial diseases (MD) are a group of rare inherited disorders, characterized by phenotypic heterogeneity, with hitherto no effective therapeutic options. The aim of this study was to develop a next generation sequencing (NGS) strategy, by using a custom gene panel and whole mitochondrial genome, to identify the disease causing pathogenic variants in 146 patients suspicious of MD. The molecular analysis of this cohort revealed six novel and 15 described pathogenic variants, as well as 26 variants of unknown significance. Our findings are expanding the mutational landscape of these disorders and support the use of a NGS strategy for a higher diagnostic yield.

摘要

线粒体疾病（MD）是一组罕见的遗传性疾病，表现出表型异质性，迄今尚无有效的治疗选择。本研究的目的是开发一种下一代测序（NGS）策略，使用定制的基因面板和整个线粒体基因组，以鉴定 146 名疑似 MD 患者的致病致病性变异。该队列的分子分析揭示了六个新的和 15 个描述的致病性变异，以及 26 个意义不明的变异。我们的发现扩大了这些疾病的突变景观，并支持使用 NGS 策略获得更高的诊断率。