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

Fiche publication

Date publication

avril 2019


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


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


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


Genet. Med.. 2019 Apr 30;: