Abstract
LISSENCEPHALY (agyria-pachygyria) is a human brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration1,2. Identification of the gene(s) involved in this disorder would facilitate molecular dissection of normal events in brain development3. Type 1 lissencephaly occurs either as an isolated abnormality or in association with dysmorphic facial appearance in patients with Miller-Dieker syndrome 4,5. 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-l as the disease gene. The deduced amino-acid sequence shows significant homology to β-subunits of heterotrimeric G proteins, suggesting that it could possibly be involved in a signal transduction pathway crucial for cerebral development.
Original language | English (US) |
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Pages (from-to) | 717-721 |
Number of pages | 5 |
Journal | Nature |
Volume | 364 |
Issue number | 6439 |
DOIs | |
State | Published - 1993 |