title: A missense mutation in theCRBNgene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family.
abstract: 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.
  
  
  
  We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members.
  
  
  
  Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members.
  
  
  
  A missense variant (c. 1171T>C) in theCRBNgene 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.
  
  
  
  These findings thus contribute to a growing list of ID disorders caused byCRBNmutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype-phenotype correlations betweenCRBNmutations and the aetiology of ARNS-ID.
authors.affiliation: Developmental Medicine Department/King Abdulaziz Medical City (KAMC)/Ministry of National Guard Health Affairs (MNG-HA), King Abdullah International Medical Research Center (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
authors.forename: Atia
authors.initials: A
authors.lastname: Sheereen
authors.affiliation: Developmental Medicine Department/King Abdulaziz Medical City (KAMC)/Ministry of National Guard Health Affairs (MNG-HA), King Abdullah International Medical Research Center (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
authors.forename: Manal
authors.initials: M
authors.lastname: Alaamery
authors.affiliation: Developmental Medicine Department/King Abdulaziz Medical City (KAMC)/Ministry of National Guard Health Affairs (MNG-HA), King Abdullah International Medical Research Center (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
authors.forename: Shahad
authors.initials: S
authors.lastname: Bawazeer
authors.affiliation: Developmental Medicine Department/King Abdulaziz Medical City (KAMC)/Ministry of National Guard Health Affairs (MNG-HA), King Abdullah International Medical Research Center (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
authors.forename: Yusra
authors.initials: Y
authors.lastname: Al Yafee
authors.affiliation: Developmental Medicine Department/King Abdulaziz Medical City (KAMC)/Ministry of National Guard Health Affairs (MNG-HA), King Abdullah International Medical Research Center (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
authors.forename: Salam
authors.initials: S
authors.lastname: Massadeh
authors.affiliation: Department of Pediatrics, King Abdulaziz Medical City (KAMC)/Ministry of National Guard-Health Affairs (MNG-HA), King Abdullah International Medical Research Center (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh , Saudi Arabia.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Eyaid
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D059472:Exome / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010447:Peptide Hydrolases / Q000235:genetics*; D012652:Self Mutilation / Q000235:genetics* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502543:CRBN protein, human; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases
keywords: ARNS-ID; CRBN gene; intellectual disability; self mutiliation; ubiquitination site