Whole-exome sequencing identifies compound heterozygous mutations in WDR62 in siblings with recurrent polymicrogyria.

TitleWhole-exome sequencing identifies compound heterozygous mutations in WDR62 in siblings with recurrent polymicrogyria.
Publication TypeJournal Article
Year of Publication2011
AuthorsMurdock, DR, Clark, GD, Bainbridge, MN, Newsham, I, Wu, Y-Q, Muzny, DM, Cheung, SWai, Gibbs, RA, Ramocki, MB
JournalAm J Med Genet A
Date Published2011 Sep
KeywordsAbnormalities, Multiple, Adult, Base Sequence, Cell Cycle Proteins, Child, Craniofacial Abnormalities, Exome, Female, Frameshift Mutation, Genetic Testing, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Magnetic Resonance Imaging, Male, Malformations of Cortical Development, Mutation, Nerve Tissue Proteins, Sequence Analysis, DNA, Sequence Deletion, Siblings

Polymicrogyria is a disorder of neuronal development resulting in structurally abnormal cerebral hemispheres characterized by over-folding and abnormal lamination of the cerebral cortex. Polymicrogyria is frequently associated with severe neurologic deficits including intellectual disability, motor problems, and epilepsy. There are acquired and genetic causes of polymicrogyria, but most patients with a presumed genetic etiology lack a specific diagnosis. Here we report using whole-exome sequencing to identify compound heterozygous mutations in the WD repeat domain 62 (WDR62) gene as the cause of recurrent polymicrogyria in a sibling pair. Sanger sequencing confirmed that the siblings both inherited 1-bp (maternal allele) and 2-bp (paternal allele) frameshift deletions, which predict premature truncation of WDR62, a protein that has a role in early cortical development. The probands are from a non-consanguineous family of Northern European descent, suggesting that autosomal recessive PMG due to compound heterozygous mutation of WDR62 might be a relatively common cause of PMG in the population. Further studies to identify mutation frequency in the population are needed.

Alternate JournalAm J Med Genet A
PubMed ID21834044
PubMed Central IDPMC3616765
Grant ListK08 NS062711 / NS / NINDS NIH HHS / United States
T32 GM007526 / GM / NIGMS NIH HHS / United States
5K08NS062711-03 / NS / NINDS NIH HHS / United States

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