title: A novel missense mutation in LIS1 in a child with subcortical band heterotopia and pachygyria inherited from his mildly affected mother with somatic mosaicism.
abstract: Mutations in the LIS1 gene result in isolated lissencephaly or subcortical band heterotopia. We report a 5-year-old male who presented with seizures and global developmental delay. Magnetic resonance imaging (MRI) demonstrated posteriorly predominant pachygyria and subcortical band heterotopia. His mother had a history of epilepsy, with onset in her teenage years. Her MRI revealed no abnormalities. Sequence analysis of the LIS1 gene identified a novel p.H389Y mutation in exon 11 (c.1165C>T). The child's mother was found to have the identical mutation as her son, with the signal intensity of the mutant allele being much lower than the normal allele, suggesting somatic mosaicism. This patient is one of only a few reported with a missense mutation in LIS1 associated with subcortical band heterotopia, and this is the first report of a mosaic individual having an affected child.
authors.affiliation: Department of Pediatrics, Division of Neurology, Children's Hospital of Eastern Ontario, Ottawa, Canada K1H 8L1. amineyko@cheo.on.ca
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mineyko
authors.forename: Asif
authors.initials: A
authors.lastname: Doja
authors.forename: Julie
authors.initials: J
authors.lastname: Hurteau
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Soma
authors.initials: S
authors.lastname: Das
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D002675:Child, Preschool; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000175:diagnosis / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D004569:Electroencephalography; D006801:Humans; D054082:Lissencephaly / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009030:Mosaicism; D020125:Mutation, Missense / Q000235:genetics*; D012640:Seizures / Q000235:genetics
chemical_list: D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human