Prevalence and architecture of de novo mutations in developmental disorders.

ABSTRACT: The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders.

SUBMITTER: Deciphering Developmental Disorders Study 

PROVIDER: S-EPMC6016744 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature