Update on novel familial forms of Parkinson's disease and multiple system atrophy

Shinsuke Fujioka, Kotaro Ogaki, Pawel M. Tacik, Ryan J. Uitti, Owen A Ross, Zbigniew K Wszolek

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Parkinson's disease (PD) and multiple system atrophy (MSA) are progressive neurodegenerative disorders classified as synucleinopathies, which are defined by the presence of α-synuclein protein pathology. Genetic studies have identified a total of 18 PARK loci that are associated with PD. The SNCA gene encodes the α-synuclein protein. The first pathogenic α-synuclein p.A53T substitution was discovered in 1997; this was followed by the identification of p.A30P and p.E46K pathogenic substitutions in 1998 and 2004, respectively. In the last year, two possible α-synuclein pathogenic substitutions, p.A18T and p.A29S, and two probable pathogenic substitutions, p.H50Q and p.G51D have been nominated. Next-generation sequencing approaches in familial PD have identified mutations in the VPS35 gene. A VPS35 p.D620N substitution remains the only confirmed pathogenic substitution. A second synucleinopathy, MSA, originally was considered a sporadic condition with little or no familial aggregation. However, recessive COQ2 mutations recently were nominated to be the genetic cause in a subset of familial and sporadic MSA cases. Further studies on the clinicogenetics and pathology of parkinsonian disorders will facilitate clarification of the molecular characteristics and pathomechanisms underlying these disorders.

Original languageEnglish (US)
JournalParkinsonism and Related Disorders
Volume20
Issue numberSUPPL.1
DOIs
StatePublished - Jan 2014

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Synucleins
Multiple System Atrophy
Parkinson Disease
Pathology
Mutation
Parkinsonian Disorders
Neurodegenerative Diseases
Genes
Proteins

Keywords

  • Familial
  • Genetics
  • MSA
  • PD
  • SNCA
  • VPS35

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Update on novel familial forms of Parkinson's disease and multiple system atrophy. / Fujioka, Shinsuke; Ogaki, Kotaro; Tacik, Pawel M.; Uitti, Ryan J.; Ross, Owen A; Wszolek, Zbigniew K.

In: Parkinsonism and Related Disorders, Vol. 20, No. SUPPL.1, 01.2014.

Research output: Contribution to journalArticle

Fujioka, Shinsuke ; Ogaki, Kotaro ; Tacik, Pawel M. ; Uitti, Ryan J. ; Ross, Owen A ; Wszolek, Zbigniew K. / Update on novel familial forms of Parkinson's disease and multiple system atrophy. In: Parkinsonism and Related Disorders. 2014 ; Vol. 20, No. SUPPL.1.
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