Isolation of a Miller-Dicker lissencephaly gene containing G protein β-subunit-like repeats

Orly Reiner, Romeo Carrozzo, Ying Shen, Manfred Wehnert, Fabrizia Faustinella, William B. Dobyns, C. Thomas Caskey, David H. Ledbetter

Research output: Contribution to journalArticlepeer-review

851 Scopus citations


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 languageEnglish (US)
Pages (from-to)717-721
Number of pages5
Issue number6439
StatePublished - 1993

Fingerprint Dive into the research topics of 'Isolation of a Miller-Dicker lissencephaly gene containing G protein β-subunit-like repeats'. Together they form a unique fingerprint.

Cite this