title: A novel WDR62 mutation causes primary microcephaly in a large consanguineous Saudi family.
abstract: BACKGROUND
  Primary microcephaly (MCPH) is a rare developmental defect characterized by impaired cognitive functions, retarded neurodevelopment and reduced brain size. It is genetically heterogeneous and more than 17 genes so far have been identified that are associated with this disease.
  
  
  OBJECTIVE
  To study the genetic defect in a consanguineous Saudi family with primary microcephaly.
  
  
  METHODS
  Cross-sectional clinical genetics study of a Saudi family.
  
  
  METHODS
  Medical genomics research center.
  
  
  METHODS
  Blood samples collected from six members of a family of healthy consanguineous parents were analyzed by whole exome sequencing to identify the underlying pathogenic mutations in two members of the family (23-year-old female and 7-year-old male) who presented with primary microcephaly, intellectual disability, delayed psychomotor development and walking difficulty, speech impedi-ments and seizures.
  
  
  METHODS
  Detection of mutation in the WD repeat domain 62 (WDR62) gene in a family segregating autosomal recessive primary microcephaly.
  
  
  RESULTS
  The exome variant analysis identified a novel missense mutation (c.3878C > A) in WDR62 gene in exon 30 resulting in amino acid change from alanine to aspartate (p.Ala1293Asp). Further validation in the affected patients and healthy members of family and 100 unrelated healthy persons as controls confirmed it to be pathogenic.
  
  
  CONCLUSIONS
  Functional impairment of the WDR62 gene can lead to severe neurodevelopmental de-fects, brain malformations and reduced head size. A missense mutation of exon 30 changed alanine to aspartate in the WDR62 protein leading to the typical MCPH phenotype.
  
  
  CONCLUSIONS
  Mutation was identified in a single family.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Naseer
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.forename: Sameera
authors.initials: S
authors.lastname: Sogaty
authors.forename: Rukhaa Adeel
authors.initials: RA
authors.lastname: Chaudhary
authors.forename: Haifa Mansour
authors.initials: HM
authors.lastname: Mansour
authors.forename: Adeel G
authors.initials: AG
authors.lastname: Chaudhary
authors.forename: Adel M
authors.initials: AM
authors.lastname: Abuzenadah
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Al-Qahtani
mesh_terms: D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins; D002648:Child; D003241:Consanguinity; D003430:Cross-Sectional Studies; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012529:Saudi Arabia; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human