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. 2011 Oct 1:11:119.
doi: 10.1186/1471-2377-11-119.

Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly

Rizwana Kousar  1 , Muhammad Jawad Hassan, Bushra Khan, Sulman Basit, Saqib Mahmood, Asif Mir, Wasim Ahmad, Muhammad Ansar
Affiliations

Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly

Rizwana Kousar et al. BMC Neurol. .

Abstract

Background: Autosomal recessive primary microcephaly is a disorder of neurogenic mitosis that causes reduction in brain size. It is a rare heterogeneous condition with seven causative genes reported to date. Mutations in WD repeat protein 62 are associated with autosomal recessive primary microcephaly with cortical malformations. This study was initiated to screen WDR62 mutations in four consanguineous Pakistani families with autosomal recessive primary microcephaly.

Methods: As part of a large study to detect the genetic basis of primary microcephaly in Pakistan, homozygosity mapping and DNA sequencing was used to explore the genetic basis of autosomal recessive primary microcephaly in four families.

Results: Four out of 100 families recruited in the study revealed linkage to the MCPH2 locus on chromosome 19, which harbor WDR62 gene. DNA sequencing in these MCPH2 linked families result in the identification of a novel nonsense mutation (p.Q648X) and three previously known mutations.

Conclusion: Our data indicate that WDR62 mutations cause about 4% of autosomal recessive primary microcephaly in Pakistan.

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Figures

Figure 1
Figure 1
Pedigrees of families MCP3, MCP26, MCP35 and MCP67 with WDR62 mutations. Clear symbols represent unaffected individuals, Filled squares represent affected males. Double lines between symbols are representatives of consanguineous unions.
Figure 2
Figure 2
The computerized tomographic (CT) scan of affected individual from family MCP67. The axial CT scan depicts ill defined gryal and nuclei pattern in the affected individual (IV-5) of family MCP67 with homozygous nonsense WDR62 mutation.
Figure 3
Figure 3
Sequence chromatograms of four probands with WDR62 mutations. A) Sequence chromatogram of family MCP67 with novel WDR62 mutation. The upper panel represents the nucleotide sequence in an affected individual, the middle panel in the heterozygous carrier and the lower panel in the unaffected individual. B) Sequence chromatogram of families MCP3, MCP26 and MCP35 with known WDR62 mutations. Arrows indicate the site of mutation.
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