Exome Sequencing in X Linked Intellectual Disability : A novel mutation in the CUL4B gene underlying Cabezas syndrome

Abstract

In this study we have applied exome sequencing of the X-chromosome in order to identify a mutation in a Finnish family with X–Linked Intellectual Disability (XLID). We identified a novel mutation in the Cullin 4B gene (CUL4B) that has previously shown to cause Cabezas syndrome. The mutation was identified using Agilent array that covers 93% of the coding region of chromosome X. The mutation is located in exon 20 resulting in premature stop codon in exon 21 where aspartic acid is changed to a premature stop codon D806X. Here we present a detailed clinical phenotype of the three affected brothers. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLID gene that encodes an E3 ubiquitin ligase. Our findings elucidate the functional significance of CUL4B in human cognition and in other aspects of human development.