Document Detail

Lrrk2 pathogenic substitutions in Parkinson's disease.
MedLine Citation:
PMID:  16172858     Owner:  NLM     Status:  MEDLINE    
Leucine-rich repeat kinase 2 (LRRK2) mutations have been implicated in autosomal dominant parkinsonism, consistent with typical levodopa-responsive Parkinson's disease. The gene maps to chromosome 12q12 and encodes a large, multifunctional protein. To identify novel LRRK2 mutations, we have sequenced 100 affected probands with family history of parkinsonism. Semiquantitative analysis was also performed in all probands to identify LRRK2 genomic multiplication or deletion. In these kindreds, referred from movement disorder clinics in many parts of Europe, Asia, and North America, parkinsonism segregates as an autosomal dominant trait. All 51 exons of the LRRK2 gene were analyzed and the frequency of all novel sequence variants was assessed within controls. The segregation of mutations with disease has been examined in larger, multiplex families. Our study identified 26 coding variants, including 15 nonsynonymous amino acid substitutions of which three affect the same codon (R1441C, R1441G, and R1441H). Seven of these coding changes seem to be pathogenic, as they segregate with disease and were not identified within controls. No multiplications or deletions were identified.
Ignacio F Mata; Jennifer M Kachergus; Julie P Taylor; Sarah Lincoln; Jan Aasly; Timothy Lynch; Mary M Hulihan; Stephanie A Cobb; Ruey-Meei Wu; Chin-Song Lu; Carlos Lahoz; Zbigniew K Wszolek; Matthew J Farrer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-09-17
Journal Detail:
Title:  Neurogenetics     Volume:  6     ISSN:  1364-6745     ISO Abbreviation:  Neurogenetics     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-30     Completed Date:  2006-08-14     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9709714     Medline TA:  Neurogenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  171-7     Citation Subset:  IM    
Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
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MeSH Terms
Gene Deletion
Genetic Variation
Middle Aged
Parkinson Disease / genetics*
Polymorphism, Genetic
Protein-Serine-Threonine Kinases / genetics*
Grant Support
Reg. No./Substance:
EC protein, human; EC Kinases

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