PMID- 26077166
OWN - NLM
STAT- MEDLINE
DCOM- 20160506
LR  - 20160707
IS  - 1873-5126 (Electronic)
IS  - 1353-8020 (Linking)
VI  - 21
IP  - 8
DP  - 2015 Aug
TI  - Early-onset parkinsonism caused by alpha-synuclein gene triplication: Clinical 
      and genetic findings in a novel family.
PG  - 981-6
LID - S1353-8020(15)00253-9 [pii]
LID - 10.1016/j.parkreldis.2015.06.005 [doi]
AB  - INTRODUCTION: Triplications of SNCA, the gene encoding for alpha-synuclein, cause a 
      very rare Mendelian form of early-onset parkinsonism combined with cognitive and 
      autonomic dysfunctions. Only six families with SNCA triplications have been 
      described so far, limiting our knowledge of the associated phenotype. In this 
      study, we report clinical and genetic findings in a new Italian family with SNCA 
      triplication. METHODS: The patients' phenotype was assessed by neurological 
      examination, neuropsychological tests, and brain imaging (MRI and SPECT-DaTSCAN). 
      For the genetic investigation, we used three independent techniques: genome-wide 
      SNP microarrays, fluorescence in situ hybridization (FISH), and multiplex 
      ligation-dependent probe amplification (MLPA). RESULTS: Genetic studies 
      documented the presence of four copies of the SNCA gene in the affected family 
      members. FISH experiments and the segregation in the family were consistent with 
      a heterozygous triplication of the SNCA locus. The patients carrying the SNCA 
      triplication developed early-onset parkinsonism combined with depression, 
      behavior disturbances, sleep disorders, and cognitive decline; marked autonomic 
      dysfunctions were not observed. Brain imaging revealed fronto-parietal atrophy 
      and a severe striatal dopaminergic deficit. CONCLUSION: The identification of 
      this novel family contributes to the genetic and clinical characterization of 
      this rare form. Our data reinforce the view that SNCA triplications cause 
      early-onset parkinsonism, with prominent non-motor features.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Olgiati, Simone
AU  - Olgiati S
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - Thomas, Astrid
AU  - Thomas A
AD  - Department of Neuroscience, Imaging, and Medical Sciences, G. d'Annunzio 
      University, Chieti/Pescara, Italy; Aging Research Centre, Ce.S.I., G. d'Annunzio 
      University Foundation, Chieti, Italy.
FAU - Quadri, Marialuisa
AU  - Quadri M
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - Breedveld, Guido J
AU  - Breedveld GJ
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - Graafland, Josja
AU  - Graafland J
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - Eussen, Hubertus
AU  - Eussen H
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - Douben, Hannie
AU  - Douben H
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - de Klein, Annelies
AU  - de Klein A
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
FAU - Onofrj, Marco
AU  - Onofrj M
AD  - Department of Neuroscience, Imaging, and Medical Sciences, G. d'Annunzio 
      University, Chieti/Pescara, Italy; Aging Research Centre, Ce.S.I., G. d'Annunzio 
      University Foundation, Chieti, Italy.
FAU - Bonifati, Vincenzo
AU  - Bonifati V
AD  - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. 
      Electronic address: v.bonifati@erasmusmc.nl.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Video-Audio Media
DEP - 20150609
PL  - England
TA  - Parkinsonism Relat Disord
JT  - Parkinsonism & related disorders
JID - 9513583
RN  - 0 (SNCA protein, human)
RN  - 0 (alpha-Synuclein)
RN  - Parkinson Disease, Familial, Type 1
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Italy
MH  - Male
MH  - Mutation
MH  - Parkinson Disease/*diagnosis/*genetics/physiopathology
MH  - Pedigree
MH  - Siblings
MH  - alpha-Synuclein/*genetics
OTO - NOTNLM
OT  - Gene
OT  - Mutation
OT  - Parkinsonism
OT  - SNCA
OT  - Triplication
OT  - alpha-synuclein
EDAT- 2015/06/17 06:00
MHDA- 2016/05/07 06:00
CRDT- 2015/06/17 06:00
PHST- 2015/03/27 00:00 [received]
PHST- 2015/05/29 00:00 [revised]
PHST- 2015/06/05 00:00 [accepted]
PHST- 2015/06/17 06:00 [entrez]
PHST- 2015/06/17 06:00 [pubmed]
PHST- 2016/05/07 06:00 [medline]
AID - S1353-8020(15)00253-9 [pii]
AID - 10.1016/j.parkreldis.2015.06.005 [doi]
PST - ppublish
SO  - Parkinsonism Relat Disord. 2015 Aug;21(8):981-6. doi: 
      10.1016/j.parkreldis.2015.06.005. Epub 2015 Jun 9.