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Frequent deletions of the LIS1 gene in classical lissencephaly

Journal Article · · American Journal of Human Genetics
OSTI ID:133659
; ;  [1]
  1. Baylor College of Medicine, Houston, TX (United States); and others

A gene on chromosome 17p associated with lissencephaly (agyriapachygyria) was recently cloned and named LIS1. We studied 38 patients with Miller-Dieker syndrome (MDS) and 59 patients with isolated lissencephaly (ILS) using chromosome analysis and fluorescence in situ hybridization (FISH) with 3 sets of overlapping cosmid probes from the 5{prime} end, the middle, and the 3{prime} end of this large gene. Among the MDS patients, cytogenetic analysis showed visible deletions or other rearrangements in 25 of 38 (66%) patients while the remainder were normal. FISH showed deletions in 24 of 26 (92%) patients tested. Among ILS patients, FISH showed deletions in 22 of 59 (37%) patients tested, but some patients were tested with only one or two probes. Deletions were found in 11 of 25 (44%) patients tested with all three FISH probes. Deletions of the 5{prime} end of the gene were detected in 24 of 26 MDS patients but in only 2 of 30 ILS patients tested. We conclude that MDS results from large deletions of the LIS1 gene, particularly those involving the 5{prime} end of the gene. ILS results from smaller deletions of the LIS1 gene in at least 44 percent of patients, which rarely involve the 5{prime} end. We expect future studies to show deletions of the LIS1 gene in well over half of all patients with classical, generalized lissencephaly.

OSTI ID:
133659
Report Number(s):
CONF-941009--
Journal Information:
American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
Country of Publication:
United States
Language:
English

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