Mutational analysis of FBXO7 gene in Parkinson's disease in a Taiwanese population.
Mutations in the FBXO7 gene cause an autosomal-recessive early-onset parkinsonism with pyramidal tract signs. Its role in typical Parkinson's disease (PD) without pyramidal features is unclear. We assayed FBXO7 gene in 900 participants comprising 448 PD patients and 452 age- and sex-matched control subjects from Taiwan. The entire FBXO7 coding region and intron-exon boundaries were sequenced. We identified 2 novel missense substitutions, p.Ile87Thr and p.Asp328Arg, in a single heterozygous state in 2 early-onset PD patients individually (1.1% early-onset PD). These 2 variants were not observed in control subjects with a total of 904 normal alleles. Additionally, we also found 1 noncoding variant, exon 1 IVS-329C>T, modestly associated with PD. The frequency of the CT/TT genotype was higher in PD patients compared with control subjects (odds ratio, 1.43; 95% confidence interval, 1.02-2.01; p = 0.04). The clinical phenotypes of genetic variant carriers are similar to that seen in idiopathic PD. We conclude that FBXO7 gene contributes little to typical PD in our population. Further studies in other ethnic cohorts will be important to address its potential pathophysiological role in PD.
Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chin-Hsien
CH
Lin
Meng-Ling
ML
Chen
Tzu-Ting
TT
Lai
Chun-Hwei
CH
Tai
Ruey-Meei
RM
Wu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D044783:F-Box Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
D044783:F-Box Proteins; C489149:FBXO7 protein, human