Analysis of Parkinson's disease brain–derived DNA for alpha‐synuclein coding somatic mutations. Issue 8 (21st April 2014)

• Record Type: Journal Article
• Authors: Proukakis, Christos; Shoaee, Maryiam; Morris, James; Brier, Timothy; Kara, Eleanna; Sheerin, Una‐Marie; Charlesworth, Gavin; Tolosa, Eduardo; Houlden, Henry; Wood, Nicholas W.; Schapira, Anthony H.
• Is Part Of: Movement disorders. Volume 29:Issue 8(2014)
• Page Start: 1060
• Page End: 1064
• Publication Date: 2014-04-21
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.25883
• Languages: English
• ISSNs: 0885-3185

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="mds25883-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="mds25883-sec-0002" sec-type="section"> <title>Methods</title> <p>Expanding on our recent negative small study, we used high‐resolution melting (HRM) analysis to screen <italic>SNCA</italic> 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.</p> </sec> <sec id="mds25883-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="mds25883-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding <italic>SNCA</italic> point mutations. © 2014 International Parkinson and Movement Disorder Society</p> </sec> </abstract>