Clinical exome sequencing uncovers a high frequency of Mendelian disorders in infants with stroke: A retrospective analysis.
Clinical exome sequencing uncovers a high frequency of Mendelian disorders in infants with stroke: A retrospective analysis.
复制标题
DOI：
10.1002/ajmg.a.62967
复制
发表时间：
2022-11
影响因子：
2
通讯作者：
Lalani, Seema R.
中科院分区：
文献类型：
--
作者：
Kumar, Runjun D.;Meng, Linyan;Liu, Pengfei;Miyake, Christina Y.;Worley, Kim C.;Bi, Weimin;Lalani, Seema R.
中风导致严重残疾，是全球常见的死亡原因。先前的研究估计，1-5%的中风可归因于单基因病因。我们着手评估临床外显子组测序（ES）在卒中评估中的实用性。我们回顾性分析了2012年至2021年期间在贝勒遗传学参考实验室接受ES的124名患者，这些患者的报告表型主要是中风。年龄从10天到69岁不等。8.9%的队列接受了诊断，包括25%的1岁以下婴儿;另外10.5%的队列接受了可能的诊断。我们确定了几种易患中风的综合征，如COL 4A 1相关的脑小血管疾病、CBS相关的同型胱氨酸尿症、POLG相关疾病、TTC 19相关的线粒体疾病和RNASEH 2A相关的Aicardi-Goutieres综合征。我们还观察到NSD 1、PKHD 1、HRAS和ATP 13 A2的致病性变异，这些基因很少与卒中相关。虽然中风是一种复杂的表型，具有不同的病理和风险因素，但这些结果表明，使用外显子组测序与中风高度相关，特别是对于那些年龄<1岁的患者。
Stroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke. We retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype. Ages ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional 10.5% of the cohort received a probable diagnosis. We identified several syndromes that predispose to stroke such as COL4A1-related brain small vessel disease, CBS-related homocystinuria, POLG-related disorders, TTC19-related mitochondrial disease, and RNASEH2A associated Aicardi-Goutieres syndrome. We also observed pathogenic variants in NSD1, PKHD1, HRAS and ATP13A2, which are genes rarely associated with stroke. Although stroke is a complex phenotype with varying pathologies and risk factors, these results show that use of exome sequencing can be highly relevant in stroke, especially for those presenting <1 year of age.
登录
查看更多内容
影响因子：
2
作者：
Gudenkauf FJ;Azamian MS;Hunter JV;Nayak A;Lalani SR
通讯作者：
Lalani SR
影响因子：
8.8
作者：
Kalia, Sarah S.;Adelman, Kathy;Miller, David T.
通讯作者：
Miller, David T.
DOI：
10.1212/01.con.0000446109.20539.68
发表时间：
2014-04-01
期刊：
Continuum (Minneapolis, Minn.)
影响因子：
--
作者：
Barrett, Kevin M;Meschia, James F
通讯作者：
Meschia, James F
影响因子：
3.5
作者：
Chojdak-Łukasiewicz J;Dziadkowiak E;Budrewicz S
通讯作者：
Budrewicz S
影响因子：
9.8
作者：
Lalani, Seema R.;Liu, Pengfei;Yang, Yaping
通讯作者：
Yang, Yaping