Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants.

Date publication

avril 2019

Journal

Genetics in medicine : official journal of the American College of Medical Genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence , Pr PHILIPPE Christophe , Dr NAMBOT Sophie

Tous les auteurs :
Lecoquierre F, Duffourd Y, Vitobello A, Bruel AL, Urteaga B, Coubes C, Garret P, Nambot S, Chevarin M, Jouan T, Moutton S, ,Tran-Mau-Them F, Philippe C, Sorlin A, Faivre L, Thauvin-Robinet C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31036916

Résumé

Next-generation sequencing has revealed the major impact of de novo variants (DNVs) in developmental disorders (DD) such as intellectual disability, autism, and epilepsy. However, a substantial fraction of these predicted pathogenic DNVs remains challenging to distinguish from background DNVs, notably the missense variants acting via nonhaploinsufficient mechanisms on specific amino acid residues. We hypothesized that the detection of the same missense variation in at least two unrelated individuals presenting with a similar phenotype could be a powerful approach to reveal novel pathogenic variants.

Mots clés

de novo variant, denovo-db, developmental disorders, exome sequencing, missense

Référence

Genet. Med.. 2019 Apr 30;: