Mutational analysis of parkin and PINK1 in multiple system atrophy.
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.
Brooks
Janet A
JA
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
Houlden
Henry
H
Melchers
Anna
A
Islam
Ansha J
AJ
Ding
Jinhui
J
Li
Abi
A
Paudel
Reema
R
Revesz
Tamas
T
Holton
Janice L
JL
Wood
Nick
N
Lees
Andrew
A
Singleton
Andrew B
AB
Scholz
Sonja W
SW
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
D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein