A novel single base pair duplication in WDR62 causes primary microcephaly

Abstract

BackgroundPrimary microcephaly is a disorder of the brain resulting in a reduced head circumference that can come along with intellectual disability but with hardly any other neurological abnormalities.Case presentationIn this study we report on three Pakistani males from a consanguineous family with 2, 4 and 25 years, diagnosed with autosomal recessive primary microcephaly. By genotyping, Sanger sequencing and using bioinformatical approaches the disease causing mutation was identified and evaluated.ConclusionBy using a 250K SNP array, we were able to detect an 11Mb large autozygous region in the MCPH2 locus on chromosome 19q13.12. Sequencing of the associated gene, WDR62, revealed the frameshift causing single base pair duplication, c.2527dupG. This mutation is predicted to affect the structural features of WDR62 which in turn changes the conformation and function of the protein. Aspartic acid (D) at position 843 was found to be conserved among various ortholog species. The present findings will be helpful in genetic diagnosis of patients and future studies of WDR62.

Novel splice‐site mutation in WDR62 revealed by whole‐exome sequencing in a Sudanese family with primary microcephaly

“…) and others (Rupp et al. ). The pathological features of these disorders are related to abnormal proliferation and migration into distinct cytoarchitectonic areas in the cerebral cortex (Bystron et al.…”

“…Autosomal recessive primary microcephaly (MCPH) is hereditary; it is evident by week 32 of gestation, present at birth and non-progressive (Finlay and Darlington 1995;Woods et al 2005). Substantial genetic heterogeneity underlies this medical condition, which was mapped to at least 13 loci so far; these include WDR62 (Bilguvar et al 2010), ASPM (Bond et al 2002) and others (Rupp et al 2014). The pathological features of these disorders are related to abnormal proliferation and migration into distinct cytoarchitectonic areas in the cerebral cortex (Bystron et al 2008).…”

Dynamic centriolar relocalization of Polo kinase and Centrobin in early mitosis primes centrosome asymmetry in fly neural stem cells

“…To this end, we analyzed Polo localization in neuroblasts depleted for Cnb ( cnb RNAi) and Wdr62 ( wdr62 mutants). Wdr62 is implicated in primary microcephaly 31,32 , and both Cnb and Wdr62 are necessary for MTOC asymmetry by regulating Polo’s and Plp’s centrosomal localization in interphase neuroblasts 18,19 . Lack of Cnb or Wdr62 did not compromise the gradual loading of Asl onto the newly formed centriole in mitotic neuroblasts and Plp localization was still highly asymmetric in favor of the mother centriole (data not shown).…”

A novel non sense mutation in WDR62 causes autosomal recessive primary microcephaly: a case report

“…Genetic heterogeneity underlies this disorder, 16 genes have been identified in MCPH; these include ASPM (MCPH1) [ 13 ], WDR62 (MCPH2) [ 14 ] and others [ 15 ]. ASPM and WDR62 are the two most common genes causative for MCPH [ 16 ].…”