FMR1 gray-zone alleles: Association with Parkinson's disease in women?

• Published in: Movement disorders Vol. 26; no. 10; pp. 1900 - 1906
• Main Authors: Hall, Deborah A., Berry-Kravis, Elizabeth, Zhang, Wenting, Tassone, Flora, Spector, Elaine, Zerbe, Gary, Hagerman, Paul J., Ouyang, Bichun, Leehey, Maureen A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2011; Wiley
• Subjects: Adult; Aged; Alleles; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; fragile X mental retardation 1; Fragile X Mental Retardation Protein - genetics; fragile X-associated tremor/ataxia syndrome; Genetic Predisposition to Disease; Genetic Testing; genetics; Humans; Male; Medical sciences; Middle Aged; Neurology; Odds Ratio; Parkinson Disease - epidemiology; Parkinson Disease - genetics; Parkinson's disease; parkinsonism; Retrospective Studies; Sex Factors; Trinucleotide Repeat Expansion - genetics; Human; Chromosome fragility; Nervous system diseases; Parkinson's disease; fragile X mental retardation 1; Fragile X-associated tremor/ataxia syndrome; Parkinson disease; Developmental disorder; Mental retardation; Cerebral disorder; Parkinsonism; genetics; Central nervous system disease; Intellectual deficiency; Degenerative disease; Fragile X syndrome; Extrapyramidal syndrome
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.23755

Carriers of fragile X mental retardation 1 repeat expansions in the premutation range (55–200 CGG repeats), especially males, often develop tremor, ataxia, and parkinsonism. These neurological signs are believed to be a result of elevated levels of expanded CGG‐repeat fragile X mental retardation 1 mRNA. The purpose of this study was to determine the prevalence of fragile X mental retardation 1 repeat expansions in a movement disorder population comprising subjects with all types of tremor, ataxia, and parkinsonism. We screened 335 consecutive patients with tremor, ataxia, or parkinsonism and 273 controls confirmed to have no movement disorders. There was no difference in fragile X mental retardation 1 premutation size expansions in the cases compared with controls. Eleven percent of the women with Parkinson's disease had fragile X mental retardation 1 gray‐zone expansions compared with 4.4% of female controls (odds ratio of 3.2; 95% confidence interval, 1.2–8.7). Gray‐zone expansions in patients with other phenotypes were not overrepresented in comparison with controls. Fragile X mental retardation 1 premutation range expansions are not more common in a mixed movement disorder population compared with controls. Our results, however, suggest that fragile X mental retardation 1 gray‐zone alleles may be associated with Parkinson's disease in women. © 2011 Movement Disorder Society