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

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

doi:10.1186/1471-2377-11-119

Abstract

BackgroundAutosomal 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.MethodsAs 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.ResultsFour 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.ConclusionOur data indicate that WDR62 mutations cause about 4% of autosomal recessive primary microcephaly in Pakistan.

Highlights

Autosomal recessive primary microcephaly is a disorder of neurogenic mitosis that causes reduction in brain size
We report identification of a novel and three known mutation in WDR62 gene in four additional Pakistani families with autosomal recessive primary microcephaly
By homozygosity mapping, four families resulted in linkage with the MCPH2 locus harboring the WDR62 gene

Summary

Introduction

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. This study was initiated to screen WDR62 mutations in four consanguineous Pakistani families with autosomal recessive primary microcephaly. Autosomal recessive primary microcephaly is a heterogeneous disorder with seven causative genes reported to date These include MICROCEPHALIN at MCPH1 [5], CDK5RAP2 at MCPH3 [6]CEP152 at MCPH4 [7], ASPM at MCPH5 [8], CENPJ at MCPH6 [6], STIL at MCPH7 [9] and WDR62 at MCPH2 [1,2,3]. WDR62 (NM_001083961) gene maps to chromosome 19q13.12 and encodes two alternative WDR62 transcripts in humans, full length transcripts comprise 32

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Conclusion