TY - JOUR
T1 - Phenotypic spectrum of alpha-synuclein mutations
T2 - New insights from patients and cellular models
AU - Petrucci, Simona
AU - Ginevrino, Monia
AU - Valente, Enza Maria
PY - 2016/1/1
Y1 - 2016/1/1
N2 - The identification of the p.A53T mutation in the SNCA gene encoding alpha-synuclein (alpha-syn), as causative of autosomal dominant Parkinson disease (PD) represented a fundamental milestone, which paved the way to the extremely prolific field of PD genetics. Despite being the oldest player in this field and only a rare cause of inherited PD, research on alpha-syn has remained incredibly active over nearly twenty decades, leading to identify alpha-syn aggregation as a key mechanism in PD pathogenesis.The past two years have witnessed new exciting findings, with the discovery of at least three novel pathogenic mutations (p.H50Q, p.G51D and p.A53E) causative of complex parkinsonian phenotypes, and the identification of additional patients carrying "old" SNCA mutations (p.A53T, p.A30P, p.E46K and whole gene multiplications), which has allowed to further expand their phenotypic spectrum. This review aims at providing a clinical and functional update on the most recent findings in alpha-syn genetics, at the same time discussing novel avenues of SNCA research such as those on somatic mutations and epigenetic mechanisms.
AB - The identification of the p.A53T mutation in the SNCA gene encoding alpha-synuclein (alpha-syn), as causative of autosomal dominant Parkinson disease (PD) represented a fundamental milestone, which paved the way to the extremely prolific field of PD genetics. Despite being the oldest player in this field and only a rare cause of inherited PD, research on alpha-syn has remained incredibly active over nearly twenty decades, leading to identify alpha-syn aggregation as a key mechanism in PD pathogenesis.The past two years have witnessed new exciting findings, with the discovery of at least three novel pathogenic mutations (p.H50Q, p.G51D and p.A53E) causative of complex parkinsonian phenotypes, and the identification of additional patients carrying "old" SNCA mutations (p.A53T, p.A30P, p.E46K and whole gene multiplications), which has allowed to further expand their phenotypic spectrum. This review aims at providing a clinical and functional update on the most recent findings in alpha-syn genetics, at the same time discussing novel avenues of SNCA research such as those on somatic mutations and epigenetic mechanisms.
KW - Alpha-synuclein
KW - Genotype-phenotype correlates
KW - Mutations
KW - SNCA
UR - http://www.scopus.com/inward/record.url?scp=84947864130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947864130&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2015.08.015
DO - 10.1016/j.parkreldis.2015.08.015
M3 - Article
C2 - 26341711
AN - SCOPUS:84947864130
VL - 22
SP - S16-S20
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -