Document Detail


Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia.
MedLine Citation:
PMID:  19050731     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Classical lissencephaly, or isolated lissencephaly sequence (ILS), and subcortical band heterotopia (SBH) are neuronal migration disorders associated with severe mental retardation and epilepsy. Abnormalities of the LIS1 and DCX genes are implicated in the majority of patients with these disorders and account for approximately 75% of patients with ILS, whereas mutations of DCX account for 85% of patients with SBH. The molecular basis of disease in patients with ILS and SBH, in whom no abnormalities have been identified, has been questioned. We studied a series of 83 patients with ILS, SBH or pachygyria, in whom no abnormalities of the LIS1 or DCX genes had been identified, for intragenic deletions and duplications by multiplex ligation-dependent probe amplification (MLPA). In 52 patients with ILS, we identified 12 deletions and 6 duplications involving the LIS1 gene (35%), with the majority resulting in grade 3 lissencephaly. Three deletions of the DCX gene were identified in the group of nine female patients with SBH (out of 31 patients with DCX-suggestive brain anomalies), ie 33%. We estimate an overall mutation detection rate of approximately 85% by LIS1 and DCX sequencing and MLPA in ILS, and 90% by DCX sequencing and MLPA in SBH. Our results show that intragenic deletions and duplications of the LIS1 and DCX genes account for a significant number of patients with ILS and SBH, where no molecular defect had previously been identified. Incorporation of deletion/duplication analysis of the LIS1 and DCX genes will be important for the molecular diagnosis of patients with ILS and SBH.
Authors:
Eden V Haverfield; Amanda J Whited; Kristin S Petras; William B Dobyns; Soma Das
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-12-03
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  17     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-18     Completed Date:  2009-10-02     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  911-8     Citation Subset:  IM    
Affiliation:
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics*
Classical Lissencephalies and Subcortical Band Heterotopias / genetics*
DNA Mutational Analysis
Female
Gene Deletion*
Gene Duplication*
Genes
Humans
Male
Microtubule-Associated Proteins / genetics*
Neuropeptides / genetics*
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
P01-NS039404/NS/NINDS NIH HHS; R01-NS058721/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Microtubule-Associated Proteins; 0/Neuropeptides; 0/doublecortin protein; EC 3.1.1.47/1-Alkyl-2-acetylglycerophosphocholine Esterase; EC 3.1.1.47/PAFAH1B1 protein, human
Comments/Corrections

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