title: Identification of DCX gene mutation in lissencephaly spectrum with subcortical band heterotopia using whole exome sequencing.
abstract: Malformations of cortical development include a wide range of brain developmental anomalies that commonly lead to developmental delay and epilepsy. Lissencephaly and subcortical band heterotopia are major malformations of cortical development due to abnormal neuronal migration and several genes have been identified including ARX, DCX, LIS1, RELN, TUBA1A, and VLDLR. Traditionally, genetic testing for lissencephaly and subcortical band heterotopia has been done in the order of the probability of detection of mutation according to the radiologic features, but the success rate could be variable with this time-consuming approach. In this study we used whole-exome sequencing to identify mutations in a 5-year-old girl with lissencephaly spectrum with subcortical band heterotopia. After excluding lissencephaly-related genes, one deleterious mutation (NM_178153.2:c.665C > T, p.Thr222Ile) in the DCX gene was identified. Further Sanger sequencing validated the variant in the patient but not in both parents indicating a de novo mutation. The present report demonstrates that whole-exome sequencing may be a useful tool for the identification of mutations in patients with lissencephaly and subcortical band heterotopias as well as malformations of cortical development.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Jang
authors.forename: Hye In
authors.initials: HI
authors.lastname: Woo
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Jeehun
authors.initials: J
authors.lastname: Lee
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
mesh_terms: D002675:Child, Preschool; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics*; D016000:Cluster Analysis; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D059472:Exome / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D015723:Gene Library; D006801:Humans; D054082:Lissencephaly / Q000235:genetics* / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics*; D010290:Parents; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000091042:Reelin Protein; D056910:Republic of Korea; D017422:Sequence Analysis, DNA
chemical_list: C000714328:DCX protein, human; D017931:DNA Primers; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; D004247:DNA; C000717127:RELN protein, human