title: Isolated lissencephaly sequence and double-cortex syndrome in a German family with a novel doublecortin mutation.
abstract: Isolated Lissencephaly Sequence (ILS) and Double-Cortex Syndrome (DC) are neuronal heterotopias caused by developmental defects in neuronal precursor cell migration. We report on the clinical and genetic assessment of a German pedigree with DCIILS. Affected males showed clinical symptoms typical of lissencephaly, i.e. seizures, severe mental retardation and extensive physical disability starting in the early postnatal period. Females, however, displayed a milder phenotype with epileptic seizures being the only clinical symptom of note. The MR imaging of a male ILS patient showed a smooth cortex with pachygyria, hydrocephalus and a diffuse, broad distribution of grey matter throughout the brain. In the affected female, a double cortex syndrome in the form of a subcortical bilateral band of grey matter was evident by MR imaging. The molecular and genetic basis of DC/ILS is associated with mutations in the X-linked doublecortin gene (DCX). The genetic assessment of the family revealed a novel missense mutation 211 G-->T in DCX exon 2 in affected family members. This mutation cosegregated with the clinical symptoms and resulted in a non-conservative amino acid substitution A71S. DCX is a microtubule-associated phosphoprotein and mutations in DCX might affect cytoskeletal dynamics and the regulation of cell migration.
authors.affiliation: Department of Neurology, VW-Foundation Junior Group, University of Regensburg, Germany. ludwig.aigner@klinik.uni-regensburg.de
authors.forename: L
authors.initials: L
authors.lastname: Aigner
authors.forename: D
authors.initials: D
authors.lastname: Fluegel
authors.forename: J
authors.initials: J
authors.lastname: Dietrich
authors.forename: S
authors.initials: S
authors.lastname: Ploetz
authors.forename: J
authors.initials: J
authors.lastname: Winkler
mesh_terms: D001921:Brain / Q000002:abnormalities*; D002540:Cerebral Cortex / Q000002:abnormalities*; D017931:DNA Primers / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D004569:Electroencephalography; D004830:Epilepsy, Tonic-Clonic / Q000175:diagnosis; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics
chemical_list: D017931:DNA Primers; D016373:DNA, Antisense