Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein

Cell. 1998 Jan 9;92(1):63-72. doi: 10.1016/s0092-8674(00)80899-5.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Brain / metabolism
  • Cerebral Cortex / abnormalities*
  • Cerebral Cortex / chemistry
  • Chromosome Fragility
  • Chromosome Mapping
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Doublecortin Domain Proteins
  • Epilepsy / genetics*
  • Family Health
  • Genes / genetics*
  • Humans
  • Microtubule-Associated Proteins*
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation / physiology
  • Neuropeptides / genetics*
  • Protein Serine-Threonine Kinases / genetics
  • Proteins / genetics
  • Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Sex Chromosome Aberrations / genetics*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Syndrome
  • Translocation, Genetic / genetics
  • Translocation, Genetic / physiology
  • X Chromosome*


  • DNA, Complementary
  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Proteins
  • Protein Serine-Threonine Kinases

Associated data

  • GENBANK/AF034634