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A novel WDR62 mutation causes primary microcephaly in a Pakistani family

Mazhar Mustafa Memon1, Syed Irfan Raza, Sulman Basit

  • 1Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Molecular Biology Reports
|October 16, 2012
PubMed

Insights

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder. A Pakistani family study identified a WDR62 gene mutation causing severe brain malformations in affected individuals.

Area of Science:

  • Genetics
  • Neuroscience
  • Developmental Biology

Background:

  • Autosomal recessive primary microcephaly (MCPH) is a heterogeneous neurodevelopmental disorder.
  • While typically associated with mild brain anomalies, some MCPH cases involve severe malformations linked to specific genes.

Purpose of the Study:

  • To investigate the genetic cause of severe brain malformations in a Pakistani family with primary microcephaly.
  • To identify the specific gene mutation responsible for the observed neurodevelopmental disorder.

Main Methods:

  • Clinical evaluation of affected individuals and family history analysis.
  • Candidate gene mapping and subsequent sequencing of the WD repeat domain 62 (WDR62) gene.
  • Mutation analysis to identify genetic variants.

Main Results:

  • Three affected individuals from a five-generation Pakistani family presented with primary microcephaly, intellectual disability, schizencephaly, and corpus callosum hypoplasia.
  • A homozygous deletion mutation (c.1143delA) in exon 9 of the WDR62 gene was identified in all affected individuals.
  • This mutation leads to a frameshift and protein truncation (p.H381PfsX48).

Conclusions:

  • The study confirms the role of WDR62 in severe brain malformations.
  • WDR62 mutations are a significant cause of autosomal recessive primary microcephaly with complex brain anomalies.
  • This finding expands the genotypic spectrum of MCPH and highlights WDR62's importance in neurodevelopment.

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