Screen for excess FMR1 premutation alleles among males with Parkinsonism

Background: Individuals with fragile X-associated tremor/ataxia syndrome frequently have associated features of parkinsonism, often leading to an initial diagnosis of Parkinson disease or other parkinsonism spectrum disorders. Parkinson disease populations may thus include individuals who harbor premutation expansions ( 55-200 CGG repeats) of the fragile X mental retardation 1 ( FMR1) gene. Objective: To screen DNA samples ( male) from an Italian Parkinson disease clinic for an excess of premutation expansions of the FMR1 gene. Design: DNA samples obtained from 903 unrelated males through consecutive clinic visits were analyzed by an enhanced polymerase chain reaction method for detecting expanded CGG repeats Setting: Diagnostic assessments were performed at the Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy. Genotyping was conducted at the University of California Davis School of Medicine. Participants: A cohort of unrelated males with clinical features of parkinsonism. All but 12 males were of Italian origin, and all reported Caucasian ethnicity. Main Outcome Measure: CGG repeat number. Results: Three premutation carriers ( 61, 69, and 80 CGG repeats) were identified ( 0.33%), which is not significantly higher than the frequency of premutation alleles in the general population. The outcome of the current study, the largest screen of individuals with parkinsonism to date, supports previous screens of smaller parkinsonism cohorts. Conclusion: Broad screening for premutation alleles in Parkinson disease populations is unlikely to be productive in the absence of additional clinical or family history data that suggest involvement of the FMR1 gene.