PMID- 16358335
OWN - NLM
STAT- MEDLINE
DCOM- 20060425
LR  - 20220321
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 59
IP  - 2
DP  - 2006 Feb
TI  - Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's 
      disease.
PG  - 298-309
AB  - 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. INTERPRETATION: 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.
FAU - Nishioka, Kenya
AU  - Nishioka K
AD  - Department of Neurology, Juntendo University School of Medicine, Hongo, Tokyo, 
      Japan.
FAU - Hayashi, Shin
AU  - Hayashi S
FAU - Farrer, Matthew J
AU  - Farrer MJ
FAU - Singleton, Andrew B
AU  - Singleton AB
FAU - Yoshino, Hiroyo
AU  - Yoshino H
FAU - Imai, Hisamasa
AU  - Imai H
FAU - Kitami, Toshiaki
AU  - Kitami T
FAU - Sato, Kenichi
AU  - Sato K
FAU - Kuroda, Ryu
AU  - Kuroda R
FAU - Tomiyama, Hiroyuki
AU  - Tomiyama H
FAU - Mizoguchi, Koichi
AU  - Mizoguchi K
FAU - Murata, Miho
AU  - Murata M
FAU - Toda, Tatsushi
AU  - Toda T
FAU - Imoto, Issei
AU  - Imoto I
FAU - Inazawa, Johji
AU  - Inazawa J
FAU - Mizuno, Yoshikuni
AU  - Mizuno Y
FAU - Hattori, Nobutaka
AU  - Hattori N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (RNA, Messenger)
RN  - 0 (alpha-Synuclein)
SB  - IM
MH  - Aged
MH  - Brain Mapping
MH  - DNA Mutational Analysis
MH  - Family Health
MH  - Female
MH  - Functional Laterality
MH  - Gene Dosage/physiology
MH  - *Gene Duplication
MH  - *Genetic Heterogeneity
MH  - Haplotypes
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Parkinson Disease/*genetics/pathology
MH  - Pedigree
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - alpha-Synuclein/*genetics
EDAT- 2005/12/17 09:00
MHDA- 2006/04/28 09:00
CRDT- 2005/12/17 09:00
PHST- 2005/12/17 09:00 [pubmed]
PHST- 2006/04/28 09:00 [medline]
PHST- 2005/12/17 09:00 [entrez]
AID - 10.1002/ana.20753 [doi]
PST - ppublish
SO  - Ann Neurol. 2006 Feb;59(2):298-309. doi: 10.1002/ana.20753.