title: Mutational analysis of parkin and PINK1 in multiple system atrophy.
abstract: Multiple system atrophy (MSA) and Parkinson's disease (PD) are progressive neurodegenerative disorders with overlapping clinical, biochemical and genetic features. To test the hypothesis that the PD genes parkin and PINK1 also play a role in the pathogenesis of MSA, we performed a mutational screening study involving 87 pathologically proven MSA cases. In parkin we identified eight sequence variants and four heterozygous deletions and in PINK1 we identified nine variants of which two silent mutations have not been previously reported (p.Gly189Gly and p.Arg337Arg). The frequencies of the observed variants were not significantly different from previously published control data and none of the possibly pathogenic variants were found in a homozygous state. Our results indicate that genetic variants at the parkin and PINK1 loci do not play a critical role in the pathogenesis of MSA.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Brooks
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Anna
authors.initials: A
authors.lastname: Melchers
authors.forename: Ansha J
authors.initials: AJ
authors.lastname: Islam
authors.forename: Jinhui
authors.initials: J
authors.lastname: Ding
authors.forename: Abi
authors.initials: A
authors.lastname: Li
authors.forename: Reema
authors.initials: R
authors.lastname: Paudel
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.forename: Nick
authors.initials: N
authors.lastname: Wood
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
mesh_terms: D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019578:Multiple System Atrophy / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein