Publication Date
11-1-2022
Journal
American Journal of Medical Genetics Part A
DOI
10.1002/ajmg.a.62967
PMID
36065636
PMCID
PMC9703357
PubMedCentral® Posted Date
11-28-2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Exome, Humans, Phenotype, Retrospective Studies, Stroke, Exome Sequencing, exome sequencing, stroke, genetic diagnosis, rare diseases
Abstract
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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Diseases Commons, Genetic Phenomena Commons, Genetic Processes Commons, Medical Genetics Commons, Pediatrics Commons