Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease.
OBJECTIVE
Recently, genomic multiplications of alpha-synuclein gene (SNCA) have been reported to cause hereditary early-onset parkinsonism. The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD).


METHODS
We screened 113 ADPD probands and 200 sporadic PD cases by quantitative polymerase chain reaction and confirmed SNCA multiplications by fluorescence in situ hybridization (FISH) and comparative genomic hybridization array.


RESULTS
Two families (two patients from Family A and one from Family B) with SNCA duplication were identified among ADPD patients. Even though they had the same SNCA duplication, one patient had dementia. Because there was exactly the same difference between the regions originated from each patient, the finding suggests that the phenotype of SNCA multiplication may be also influenced by the range of duplication region. We also detected asymptomatic carriers in the families of both patients. Interestingly, the penetrance ratio was 33.3% (2/6) in one kindred, indicating that the ratio was very much lower than expected.


CONCLUSIONS
These two newly identified Japanese patients with SNCA duplication and the five previously identified American and European families with SNCA triplication or duplication mutations indicate that the incidence of SNCA multiplication may be more frequent than previously estimated.
Nishioka
Kenya
K
Department of Neurology, Juntendo University School of Medicine, Hongo, Tokyo, Japan.
Hayashi
Shin
S
Farrer
Matthew J
MJ
Singleton
Andrew B
AB
Yoshino
Hiroyo
H
Imai
Hisamasa
H
Kitami
Toshiaki
T
Sato
Kenichi
K
Kuroda
Ryu
R
Tomiyama
Hiroyuki
H
Mizoguchi
Koichi
K
Murata
Miho
M
Toda
Tatsushi
T
Imoto
Issei
I
Inazawa
Johji
J
Mizuno
Yoshikuni
Y
Hattori
Nobutaka
N
D000368:Aged; D001931:Brain Mapping; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D007839:Functional Laterality; D018628:Gene Dosage / Q000502:physiology; D020440:Gene Duplication; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051844:alpha-Synuclein / Q000235:genetics*
D012333:RNA, Messenger; D051844:alpha-Synuclein