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Isolated lissencephaly sequence and double-cortex syndrome in a German family with a novel doublecortin mutation

L Aigner, Dominique Flügel, J Dietrich, S Ploetz & J Winkler

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.
   
citation Aigner L, Flügel D, Dietrich J, Ploetz S, Winkler J. Isolated lissencephaly sequence and double-cortex syndrome in a German family with a novel doublecortin mutation. Neuropediatrics 2000; 31:195-8.
   
type journal paper/review (English)
date of publishing 8-2000
journal title Neuropediatrics (31/4)
ISSN print 0174-304X
pages 195-8
PubMed 11071144
DOI 10.1055/s-2000-7452