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

Nature volume 364, pages 717–721 (1993)Cite this article

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 syndrome4,5. 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.

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Authors and Affiliations

  1. Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

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

  2. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, 77030, USA

    C. Thomas Caskey

  3. Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, 55455, USA

    William B. Dobyns

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  1. Orly Reiner
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  2. Romeo Carrozzo
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Reiner, O., Carrozzo, R., Shen, Y. et al. Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats. Nature 364, 717–721 (1993). https://doi.org/10.1038/364717a0

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