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Analysis of Parkinson's disease brain–derived DNA for alpha‐synuclein coding somatic mutations
Author(s) -
Proukakis Christos,
Shoaee Maryiam,
Morris James,
Brier Timothy,
Kara Eleanna,
Sheerin UnaMarie,
Charlesworth Gavin,
Tolosa Eduardo,
Houlden Henry,
Wood Nicholas W.,
Schapira Anthony H.
Publication year - 2014
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25883
Subject(s) - substantia nigra , alpha synuclein , biology , somatic cell , parkinson's disease , genetics , point mutation , dementia with lewy bodies , mutation , neuroscience , gene , pathology , disease , medicine , dementia
Background Although alpha‐synuclein (SNCA) is crucial to the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), mutations in the gene appear to be rare. We have recently hypothesized that somatic mutations in early development could contribute to PD. Methods Expanding on our recent negative small study, we used high‐resolution melting (HRM) analysis to screen SNCA coding exons for somatic point mutations in DNA from 539 PD and DLB cerebellar samples, with two additional regions (frontal cortex, substantia nigra) for 20 PD cases. We used artificial mosaics to determine sensitivity where possible. Results We did not detect any evidence of somatic coding mutations. Three cases were heterozygous for known silent polymorphisms. The protocol we used was sensitive enough to detect 5% to 10% mutant DNA. Conclusion Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding SNCA point mutations. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.