1. doublecortin, a Brain-Specific Gene Mutated in Human X-Linked Lissencephaly and Double Cortex Syndrome, Encodes a Putative Signaling Protein
- Author
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William B. Dobyns, Joseph G. Gleeson, Christopher A. Walsh, M. Elizabeth Ross, Sharon R. Minnerath, Samuel F. Berkovic, Jeremy W. Fox, Ingrid E. Scheffer, Edward D Lamperti, Edward C. Cooper, and Kristina M. Allen
- Subjects
Doublecortin Domain Proteins ,DNA, Complementary ,X Chromosome ,Molecular Sequence Data ,Lissencephaly ,Protein Serine-Threonine Kinases ,Type I lissencephaly ,Translocation, Genetic ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,PAFAH1B1 ,0302 clinical medicine ,Cortex (anatomy) ,medicine ,Humans ,Amino Acid Sequence ,Sex Chromosome Aberrations ,030304 developmental biology ,Cerebral Cortex ,Family Health ,0303 health sciences ,Epilepsy ,ABL ,Base Sequence ,Sequence Homology, Amino Acid ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,Chromosome Fragility ,Neuropeptides ,Brain ,Chromosome Mapping ,Proteins ,Syndrome ,medicine.disease ,Molecular biology ,3. Good health ,Doublecortin ,medicine.anatomical_structure ,Genes ,nervous system ,Mutation ,biology.protein ,Phosphorylation ,Signal transduction ,Microtubule-Associated Proteins ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin. Four double cortex/X-linked lissencephaly families and three sporadic double cortex patients show independent doublecortin mutations, at least one of them a de novo mutation. Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin does not contain a kinase domain, it is homologous to the amino terminus of a predicted kinase protein, indicating a likely role in signal transduction. Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration.
- Published
- 1998
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