Details

Autor(en) / Beteiligte

• Martin, Hilary C
• Gardner, Eugene J
• Samocha, Kaitlin E
• Kaplanis, Joanna
• Akawi, Nadia
• Sifrim, Alejandro
• Eberhardt, Ruth Y
• Tavares, Ana Lisa Taylor
• Neville, Matthew D C
• Niemi, Mari E K
• Gallone, Giuseppe
• McRae, Jeremy
• Wright, Caroline F
• FitzPatrick, David R
• Firth, Helen V
• Hurles, Matthew E

Titel

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

Ist Teil von

• Nature communications, 2021-01, Vol.12 (1), p.627-627, Article 627

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.