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@ARTICLE{Alefanti:276324,
author = {Alefanti, Ioanna and Koros, Christos and Tsami, Viktoria
and Simitsi, Athina Maria and Kartanou, Chrisoula and
Papagiannakis, Nikolaos and Bozi, Maria and Antonelou,
Roubina and Maniati, Matina and Hauser, Ann-Kathrin and
Varvaressos, Stefanos and Bonakis, Anastasios and
Lourentzos, Konstantinos and Makrythanasis, Periklis and
Papageorgiou, Sokratis G and Proukakis, Christos and
Potagas, Constantinos and Gasser, Thomas and Koutsis,
Georgios and Karadima, Georgia and Stefanis, Leonidas},
title = {{T}he novel p.{A}30{G} {SNCA} pathogenic variant in {G}reek
patients with familial and sporadic {P}arkinson's disease.},
journal = {European journal of neurology},
volume = {32},
number = {2},
issn = {1351-5101},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2025-00287},
pages = {e16562},
year = {2025},
abstract = {The p.A53T variant in the SNCA gene was considered, until
recently, to be the only SNCA variant causing familial
Parkinson's disease (PD) in the Greek population. We
identified a novel heterozygous p.A30G (c.89 C>G) SNCA
pathogenic variant in five affected individuals of three
Greek families, leading to autosomal dominant PD. This study
aims to further explore the presence and phenotypic
expression of this variant in the Greek PD
population.Restriction fragment length polymorphism (RFLPs)
was used for genotyping of 664 Greek PD cases. Detailed
clinical information was obtained for the carriers and
p.A30G-positive samples underwent haplotype analysis.We
identified 10 additional p.A30G-positive PD patients
$(1.5\%),$ of whom 4 were sporadic cases $(0.9\%).$ They
manifested typical Parkinsonian motor dysfunction, with a
mean age of onset of 51.7 years (range: 33-62) and a broad
spectrum of non-motor symptoms. The absence of affected
first degree relatives in four out of ten index cases, and
the presence of a phenocopy in an additional family, suggest
that the p.A30G variant manifests reduced penetrance. The
common haplotype among the p.A30G carriers confirmed a
founder effect. Furthermore, two asymptomatic carriers were
identified, with possible premotor manifestations.These
findings underscore that the p.A30G SNCA pathogenic variant
represents an important, albeit rare, cause of genetic PD in
the Greek population. This is the first time in which a
genetic synucleinopathy, with a variant in the SNCA gene, is
clearly linked to an appreciable frequency of sporadic PD in
a particular population.},
keywords = {Humans / alpha-Synuclein: genetics / Parkinson Disease:
genetics / Greece / Male / Middle Aged / Female / Adult /
Aged / Pedigree / Haplotypes / Genetic Predisposition to
Disease: genetics / SNCA (Other) / Greek population (Other)
/ Parkinson's disease (Other) / p.A30G (Other) /
alpha-Synuclein (NLM Chemicals) / SNCA protein, human (NLM
Chemicals)},
cin = {AG Gasser / ICRU},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)1240005},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 899 -
ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39878395},
doi = {10.1111/ene.16562},
url = {https://pub.dzne.de/record/276324},
}