The contribution of X-linked coding variation to severe developmental disorders

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Deciphering Dev Disorders , Martin , H C , Gardner , E J , Samocha , K E , Niemi , M E K & Hurles , M E 2021 , ' The contribution of X-linked coding variation to severe developmental disorders ' , Nature Communications , vol. 12 , no. 1 , 627 .

Title: The contribution of X-linked coding variation to severe developmental disorders
Author: Deciphering Dev Disorders; Martin, Hilary C.; Gardner, Eugene J.; Samocha, Kaitlin E.; Niemi, Mari E. K.; Hurles, Matthew E.
Contributor organization: Data Science Genetic Epidemiology Lab
Institute for Molecular Medicine Finland
University of Helsinki
Date: 2021-01-27
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders. Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to similar to 6% of both male and female cases and therefore does not solely explain male bias in DDs.
1184 Genetics, developmental biology, physiology
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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