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Clinical Exome Sequencing Uncovers a High Frequency of Mendelian Disorders in Infants With Stroke: A Retrospective Analysis

Title: Clinical Exome Sequencing Uncovers a High Frequency of Mendelian Disorders in Infants With Stroke: A Retrospective Analysis
Authors: Kumar, Runjun D; Meng, Linyan; Liu, Pengfei; Miyake, Christina Y; Worley, Kim C; Bi, Weimin; Lalani, Seema R
Source: Faculty and Staff Publications
Publisher Information: DigitalCommons@TMC
Publication Year: 2022
Collection: Houston Academy of Medicine-Texas Medical Center (HAM-TMC): DigitalCommons@The Texas Medical Center
Subject Terms: Exome; Humans; Phenotype; Retrospective Studies; Stroke; Exome Sequencing; genetic diagnosis; rare diseases; Diseases; Genetic Phenomena; Genetic Processes; Medical Genetics; Medical Sciences; Medical Specialties; Medicine and Health Sciences; Pediatrics
Description: 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
Document Type: text
File Description: application/pdf
Language: English
Relation: https://digitalcommons.library.tmc.edu/baylor_docs/2970; https://digitalcommons.library.tmc.edu/context/baylor_docs/article/3946/viewcontent/nihms_1848117.pdf
DOI: 10.1002/ajmg.a.62967
Availability: https://digitalcommons.library.tmc.edu/baylor_docs/2970; https://doi.org/10.1002/ajmg.a.62967; https://digitalcommons.library.tmc.edu/context/baylor_docs/article/3946/viewcontent/nihms_1848117.pdf
Accession Number: edsbas.3BE5A4BA
Database: BASE