Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.
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.
Gleeson
J G
JG
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Allen
K M
KM
Fox
J W
JW
Lamperti
E D
ED
Berkovic
S
S
Scheffer
I
I
Cooper
E C
EC
Dobyns
W B
WB
Minnerath
S R
SR
Ross
M E
ME
Walsh
C A
CA
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000737:chemistry; D002873:Chromosome Fragility; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D004827:Epilepsy / Q000235:genetics*; D005192:Family Health; D005796:Genes / Q000235:genetics*; D006801:Humans; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013577:Syndrome; D014178:Translocation, Genetic / Q000235:genetics / Q000502:physiology; D014960:X Chromosome
D018076:DNA, Complementary; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D011506:Proteins; D017346:Protein Serine-Threonine Kinases