A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features.

ABSTRACT:

Background

Intellectual disability (ID) is a common condition with a population prevalence frequency of 1-3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among the more than 500 genes associated with ID, DDX3X represents an outlier in sex specificity. Nearly all reported pathogenic variants of DDX3X are de novo, affect mostly females, and appear to be loss of function variants, consistent with the hypothesis that haploinsufficiency at this locus on the X-chromosome is likely to be lethal in males.

Results

We evaluated two male siblings with syndromic features characterized by mild-to-moderate ID and progressive spasticity. Quad-based whole-exome sequencing revealed a maternally inherited missense variant encoding p.R7

SUBMITTER: Kellaris G 

PROVIDER: S-EPMC5831694 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature