Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome.
The hexanucleotide expanded repeat (GGGGCC) in intron 1 of the C9orf72 gene is recognized as the most common genetic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, as part of the clinical phenotype, some patients present with parkinsonism. The present study investigated the potential expansion or association of the C9orf72 repeat length with susceptibility to Parkinson's disease and related disorders, essential tremor and restless legs syndrome. One restless legs syndrome patient was shown to harbor a repeat expansion, however on clinical follow-up this patient was observed to have developed frontotemporal dementia. There was no evidence of association of repeat length on disease risk or age-at-onset for any of the three disorders. Therefore the C9orf72 hexanucleotide repeat expansion appears to be specific to TDP-43 driven amyotrophic lateral sclerosis and dementia.
Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Mariely
M
Dejesus-Hernandez
Sruti
S
Rayaprolu
Alexandra I
AI
Soto-Ortolaza
Nicola J
NJ
Rutherford
Michael G
MG
Heckman
Sharleen
S
Traynor
Audrey
A
Strongosky
Neill
N
Graff-Radford
Jay
J
Van Gerpen
Ryan J
RJ
Uitti
Jerry J
JJ
Shih
Siong-Chi
SC
Lin
Zbigniew K
ZK
Wszolek
Rosa
R
Rademakers
Owen A
OA
Ross
D017668:Age of Onset; D000368:Aged; D000073885:C9orf72 Protein; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012148:Restless Legs Syndrome / Q000235:genetics*; D018911:Trinucleotide Repeats
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins