SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies

Abstract

The authors recently have shown that triplication of the alpha-synuclein gene (SNCA) can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. The authors assessed 101 familial PD probands, 325 sporadic PD cases, 65 patients with dementia with Lewy bodies, and 366 neurologically normal control subjects for SNCA multiplication. The authors did not identify any subjects with multiplication of SNCA and conclude this mutation is a rare cause of disease.

Clinical heterogeneity of α‐synuclein gene duplication in Parkinson's disease

“…22,28,29 In this study, we detected SNCA duplication in PD patients from 2 of 113 unrelated Japanese families with autosomal dominant parkinsonism. Thus, the incidence of SNCA multiplication may be more frequent than previously estimated.…”

“…The mutation screening was performed as described previously. 22 Semiquantitative multiplex polymerase chain reaction (PCR) of genomic DNA samples was performed using a real-time PCR method to detect the dosage of SNCA (ABI Prism 7700 sequence detector; Applied Biosystems, Foster City, CA). As the first step, we targeted exon 3 of SNCA to screen the gene dosage of SNCA.…”

Genetische Aspekte der REM-Schlaf-Verhaltensstörung

“…Dieses gilt in erster Linie für die idiopathischen Synukleopathien. In Assiziation mit dem erblichen Parkinson-Syndrom (s. Übersicht in [18]), dem PARK1-Syndrom, das durch eine Mutation im SynukleinGen hervorgerufen wird [19], finden sich auch Patienten, die eine nächtliche RBD aufweisen [16,17]. In den untersuchten Familien konnte jedoch anamnestisch nicht eindeutig gezeigt werden, dass die RBD eindeutig mit der Mutation im Synuklein-Gen segregiert (.…”

Parkinson disease: Insights in clinical, genetic and pathological features of monogenic disease subtypes

“…Abbreviations: SNCA: synuclein-alpha gene; PARK2: parkin gene; UCHL1: ubiquitin carboxyl-terminal esterase L1 gene; PINK1: PTEN-induced putative kinase 1 gene; DJ-1: oncogene DJ-1; LRRK2: leucine-rich repeat kinase 2 gene; ATP13A2: ATPase type 13A2 gene; GIGYF2: GRB10-interacting GYF protein 2 gene; HTRA2: HTRA serine peptidase 2 gene; PLA2G6: phospholipase A2 group 6 gene; FBXO7: F-BOX only protein 7 gene; AD: autosomal dominant; AR: autosomal recessive. While the three missense mutations in SNCA are very rare, multiplication of the gene appears to be a marginally more common cause of PD Johnson et al, 2004;Nuytemans et al, 2010). Duplication of SNCA is mostly associated with the familial occurrence of a classical PD phenotype but is marked by an earlier onset age compared to sporadic PD (Ibanez et al, 2004;Chartier-Harlin et al, 2004;Nishioka et al, 2006Nishioka et al, , 2009Nuytemans et al, 2009).…”