Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats

Nature. 1993 Aug 19;364(6439):717-21. doi: 10.1038/364717a0.


Lissencephaly (agyria-pachygyria) is a human brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration. Identification of the gene(s) involved in this disorder would facilitate molecular dissection of normal events in brain development. Type 1 lissencephaly occurs either as an isolated abnormality or in association with dysmorphic facial appearance in patients with Miller-Dieker syndrome. About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref. 6). These deletions are hemizygous, so haplo-insufficiency for a gene in this interval is implicated. Here we report the cloning of a gene (LIS-1, lissencephaly-1) in 17p13.3 that is deleted in Miller-Dieker patients. Non-overlapping deletions involving either the 5' or 3' end of the gene were found in two patients, identifying LIS-1 as the disease gene. The deduced amino-acid sequence shows significant homology to beta-subunits of heterotrimeric G proteins, suggesting that it could possibly be involved in a signal transduction pathway crucial for cerebral development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / abnormalities*
  • Chromosomes, Human, Pair 17
  • Cloning, Molecular
  • Congenital Abnormalities / genetics
  • GTP-Binding Proteins / genetics*
  • Humans
  • Hybrid Cells
  • In Situ Hybridization, Fluorescence
  • Mice
  • Molecular Sequence Data
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • GTP-Binding Proteins

Associated data

  • GENBANK/L13385
  • GENBANK/L13386
  • GENBANK/L13387
  • GENBANK/L13388