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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Brain / metabolism
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Cerebral Cortex / abnormalities*
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Cerebral Cortex / chemistry
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Chromosome Fragility
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Chromosome Mapping
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Doublecortin Domain Proteins
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Epilepsy / genetics*
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Family Health
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Genes / genetics*
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Humans
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Microtubule-Associated Proteins*
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Molecular Sequence Data
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Mutation / genetics
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Mutation / physiology
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Neuropeptides / genetics*
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Protein Serine-Threonine Kinases / genetics
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Proteins / genetics
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Proteins / physiology*
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Sequence Homology, Amino Acid
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Sex Chromosome Aberrations / genetics*
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Signal Transduction / genetics
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Signal Transduction / physiology
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Syndrome
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Translocation, Genetic / genetics
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Translocation, Genetic / physiology
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X Chromosome*
Substances
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DNA, Complementary
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Doublecortin Domain Proteins
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Microtubule-Associated Proteins
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Neuropeptides
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Proteins
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Protein Serine-Threonine Kinases