title: A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.
abstract: X-SCLH/LIS syndrome is a neuronal migration disorder with disruption of the six-layered neocortex. It consists of subcortical laminar heterotopia (SCLH, band heterotopia, or double cortex) in females and lissencephaly (LIS) in males, leading to epilepsy and cognitive impairment. We report the characterization of a novel CNS gene encoding a 40 kDa predicted protein that we named Doublecortin and the identification of mutations in four unrelated X-SCLH/LIS cases. The predicted protein shares significant homology with the N-terminal segment of a protein containing a protein kinase domain at its C-terminal part. This novel gene is highly expressed during brain development, mainly in fetal neurons including precursors. The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion.
authors.affiliation: INSERM U129-ICGM, Faculté de Médecine Cochin, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: des Portes
authors.forename: J M
authors.initials: JM
authors.lastname: Pinard
authors.forename: P
authors.initials: P
authors.lastname: Billuart
authors.forename: M C
authors.initials: MC
authors.lastname: Vinet
authors.forename: A
authors.initials: A
authors.lastname: Koulakoff
authors.forename: A
authors.initials: A
authors.lastname: Carrié
authors.forename: A
authors.initials: A
authors.lastname: Gelot
authors.forename: E
authors.initials: E
authors.lastname: Dupuis
authors.forename: J
authors.initials: J
authors.lastname: Motte
authors.forename: Y
authors.initials: Y
authors.lastname: Berwald-Netter
authors.forename: M
authors.initials: M
authors.lastname: Catala
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: C
authors.initials: C
authors.lastname: Beldjord
authors.forename: J
authors.initials: J
authors.lastname: Chelly
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000737:chemistry; D002675:Child, Preschool; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D018076:DNA, Complementary / Q000032:analysis / Q000302:isolation & purification; D000089622:Doublecortin Domain Proteins; D004827:Epilepsy / Q000235:genetics*; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005796:Genes / Q000235:genetics*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics*; D010375:Pedigree; D010455:Peptides / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D016324:Sequence Tagged Sites; D012729:Sex Chromosome Aberrations / Q000235:genetics; D013577:Syndrome; D014158:Transcription, Genetic / Q000235:genetics; D014960:X Chromosome
chemical_list: D018076:DNA, Complementary; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010455:Peptides