RT Journal Article SR Electronic T1 A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 236 OP 240 DO 10.1136/jmedgenet-2016-104117 VO 54 IS 4 A1 Atia Sheereen A1 Manal Alaamery A1 Shahad Bawazeer A1 Yusra Al Yafee A1 Salam Massadeh A1 Wafaa Eyaid YR 2017 UL http://jmg.bmj.com/content/54/4/236.abstract AB Background Autosomal-recessive non-syndromic intellectual disability (ARNS-ID) is an aetiologically heterogeneous disorder. Although little is known about the function of human cereblon (CRBN), its relationship to mild cognitive deficits suggests that it is involved in the basic processes of human memory and learning.Objectives We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members.Methods Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members.Results A missense variant (c. 1171T>C) in the CRBN gene was identified in five individuals with severe intellectual disability (ID) in a consanguineous Saudi family. The homozygous variant was co-segregating in the family with the phenotype of severe ID, seizures and self-mutilating behaviour. The missense mutation (p.C391R) reported here results in the replacement of a conserved cysteine residue by an arginine in the CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide) domain of CRBN, which contains a zinc-binding site.Conclusions These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype–phenotype correlations between CRBN mutations and the aetiology of ARNS-ID.