• Muhammad Imran Naseer, Mahmood Rasool, Sameera Sogaty, Rukhaa Adeel Chaudhary, Haifa Mansour Mansour, Adeel G Chaudhary, Adel M Abuzenadah, and Mohammad H Al-Qahtani.
• Ann Saudi Med. 2017 Mar 1; 37 (2): 148-153.

BackgroundPrimary 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.ObjectiveTo study the genetic defect in a consanguineous Saudi family with primary microcephaly.DesignCross-sectional clinical genetics study of a Saudi family.SettingMedical genomics research center.Patients And MethodsBlood 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.Main Outcome Measure(S)Detection of mutation in the WD repeat domain 62 (WDR62) gene in a family segregating autosomal recessive primary microcephaly.ResultsThe 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.ConclusionsFunctional 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.LimitationsMutation was identified in a single family.

20 keywords...

hide…