title: Screening for the presence of FMR1 premutation alleles in women with parkinsonism.
abstract: BACKGROUND
  Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive, late-onset neurodegenerative disease that affects older carriers of premutation (CGG) repeat expansions of the fragile X mental retardation 1 (FMR1) gene. Clinical features include intention tremor, gait ataxia, memory loss, peripheral neuropathy, autonomic dysfunction, and parkinsonism. The presence of parkinsonism in FXTAS raises the possibility that some individuals who have Parkinson disease are actually carriers of a premutation FMR1 allele.
  
  
  OBJECTIVE
  To screen DNA samples from a large cohort of females with Parkinson disease for an excess of expanded alleles of the FMR1 gene.
  
  
  METHODS
  We screened a cohort of 595 women with parkinsonism, the largest screening of a parkinsonism-associated group to date, for the presence of an FMR1 premutation allele (55-200 CGG repeats). The screening protocol uses an enhanced polymerase chain reaction method capable of flagging any FMR1 expanded CGG repeat in women as well as in men.
  
  
  METHODS
  Diagnostic assessments were performed at an outpatient tertiary clinic (Parkinson Institute, Milan). Genotyping was conducted at the University of California, Davis.
  
  
  METHODS
  CGG repeat number and clinical/neuroimaging assessments of patients with Parkinson disease were conducted. Two premutation carriers were identified.
  
  
  RESULTS
  Two individuals possessed an FMR1 allele in the premutation range (CGG repeats: 30 and 75; 30 and 115). This carrier frequency (2 of 595 [0.34%]) is not significantly different from estimates of the allele frequency among women in the general population (0.4%-0.8%). Clinical and radiologic features of these 2 patients were similar to those of the general Parkinson disease population; however, 1 patient (115 CGG repeats) had a family history of 2 sons with the fragile X syndrome.
  
  
  CONCLUSIONS
  Screening of women within the parkinsonism clinical spectrum is unlikely to be productive in the absence of additional medical or family history suggestive of involvement of the FMR1 gene.
authors.affiliation: Parkinson Institute-Clinici di Perfezionamento, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cilia
authors.forename: Jeremy
authors.initials: J
authors.lastname: Kraff
authors.forename: Margherita
authors.initials: M
authors.lastname: Canesi
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.forename: Khalid
authors.initials: K
authors.lastname: Amiri
authors.forename: Hiu-Tung
authors.initials: HT
authors.lastname: Tang
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Pan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D005819:Genetic Markers; C497683:FMR1 protein, human