A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency.

ABSTRACT: Genotype-first combined with reverse phenotyping has shown to be a powerful tool in human genetics, especially in the era of next generation sequencing. This combines the identification of individuals with mutations in the same gene and linking these to consistent (endo)phenotypes to establish disease causality. We have performed a MIP (molecular inversion probe)-based targeted re-sequencing study in 3,275 individuals with intellectual disability (ID) to facilitate a genotype-first approach for 24 genes previously implicated in ID.Combining our data with data from a publicly available database, we confirmed 11 of these 24 genes to be relevant for ID. Amongst these, PHIP was shown to have an enrichment of disruptive mutations in the individuals with ID (5 out of 3,275). Through internationa

SUBMITTER: Jansen S 

PROVIDER: S-EPMC5839042 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature