title: Whole-exome sequencing identifies compound heterozygous mutations in WDR62 in siblings with recurrent polymicrogyria.
abstract: 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.
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Murdock
authors.forename: Gary D
authors.initials: GD
authors.lastname: Clark
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Bainbridge
authors.forename: Irene
authors.initials: I
authors.lastname: Newsham
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Wu
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Ramocki
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D019465:Craniofacial Abnormalities / Q000235:genetics; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D035781:Siblings
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human