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Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations

Bhat, V and Girimaji, SC and Mohan, G and Arvinda, HR and Singhmar, P and Duvvari, MR and Kumar, A (2011) Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations. In: Clinical Genetics, 80 (6). pp. 532-540.

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Official URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1399-...


Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus.

Item Type: Journal Article
Publication: Clinical Genetics
Publisher: John Wiley & Sons
Additional Information: Copyright of this article belongs to John Wiley & Sons.
Keywords: centrosome;cortical malformations;Indian families;MCPH; MCPH2;WDR62
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 01 Dec 2011 10:25
Last Modified: 01 Dec 2011 10:25
URI: http://eprints.iisc.ac.in/id/eprint/42396

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