Document Detail


Clinical and molecular basis of classical lissencephaly: Mutations in the LIS1 gene (PAFAH1B1).
MedLine Citation:
PMID:  11754098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Classical lissencephaly (LIS) and subcortical band heterotopia (SBH) are related cortical malformations secondary to abnormal migration of neurons during early brain development. Approximately 60% of patients with classical LIS, and one patient with atypical SBH have been found to have deletions or mutations of the LIS1 gene, located on 17p13.3. This gene encodes the LIS1 or PAFAH1B1 protein with a coiled-coil domain at the N-terminus and seven WD40 repeats at the C-terminus. It is highly conserved between species and has been shown to interact with multiple proteins involved with cytoskeletal dynamics, playing a role in both cellular division and motility, as well as the regulation of brain levels of platelet activating factor. Here we report 65 large deletions of the LIS1 gene detected by FISH and 41 intragenic mutations, including four not previously reported, the majority of which have been found as a consequence of the investigation of 220 children with LIS or SBH by our group. All intragenic mutations are de novo, and there have been no familial recurrences. Eight-eight percent (36/41) of the mutations result in a truncated or internally deleted protein-with missense mutations found in only 12% (5/41) thus far. Mutations occurred throughout the gene except for exon 7, with clustering of three of the five missense mutations in exon 6. Only five intragenic mutations were recurrent. In general, the most severe LIS phenotype was seen in patients with large deletions of 17p13.3, with milder phenotypes seen with intragenic mutations. Of these, the mildest phenotypes were seen in patients with missense mutations.
Authors:
Carlos Cardoso; Richard J Leventer; James J Dowling; Heather L Ward; June Chung; Kristin S Petras; Jessica A Roseberry; Ann M Weiss; Soma Das; Christa Lese Martin; Daniela T Pilz; William B Dobyns; David H Ledbetter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Human mutation     Volume:  19     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-25     Completed Date:  2002-02-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4-15     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Affiliation:
Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Alkyl-2-acetylglycerophosphocholine Esterase
Animals
Brain / abnormalities*,  pathology
Disease Models, Animal
Humans
Microtubule-Associated Proteins / genetics*
Mutation / genetics*
Syndrome
Grant Support
ID/Acronym/Agency:
P01 NS39404/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Microtubule-Associated Proteins; EC 3.1.1.47/1-Alkyl-2-acetylglycerophosphocholine Esterase; EC 3.1.1.47/PAFAH1B1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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