Screening for FMR1 expanded alleles in patients with parkinsonism in mainland China.
ABSTRACT Expanded alleles of the fragile X mental retardation 1 (FMR1) gene are generally divided into four classes based on the abundance of unstable CGG repeat expansions (CGGs) in its 5'-untranslated region. It has recently been reported that two of the four classes, premutation (55-200 CGGs) and gray zone (GZ, 40-54 CGGs) alleles, was potentially associated with parkinsonism. To investigate this association in patients in mainland China, a total of 360 Chinese patients with parkinsonism and 295 gender and age matched controls were recruited in this study. Indeed, no premutation or full mutation alleles (>200 CGGs) was detected among all the subjects. A total of 11 patients with parkinsonism were identified to have GZ alleles compared with only 1 carrier among the controls (P<0.05). Notably, 10 of the 11 GZ alleles carriers with parkinsonism were female, which was 6.8% of all 147 female patients compared with none in the control females (P<0.05). No significant difference was detected between the male groups of patients and controls. Therefore, our results indicate that FMR1 GZ allele is potentially associated with parkinsonism in mainland China, and the association is only present in the female patients, but not in the male.
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ABSTRACT: Fragile X-associated tremor ataxia syndrome (FXTAS) is a recently identified X-linked neurodegenerative disorder affecting a proportion of premutation carriers of the Fragile X Mental Retardation 1 (FMR1) gene. Previous research suggests that cognitive and psychiatric features of FXTAS may include primary impairments in executive function and increased vulnerability to mood and anxiety disorders. A number of these reports, however, are based on overlapping cohorts or have produced inconsistent findings. A systematic review was therefore conducted to further elucidate the neuropsychiatric features characteristic of FXTAS. Fourteen papers met inclusion criteria for the review and were considered to represent nine independent FXTAS cohorts. Findings from the review suggest that the neuropsychiatric phenotype of FXTAS is characterised primarily by poorer performance on measures of executive function, working memory, information processing speed, and fine motor control when compared to matched comparison groups. Two studies were identified in which psychiatric symptoms in FXTAS were compared with controls, and these yielded mixed results. Overall the results of this review support previous reports that the neuropsychiatric profile of FXTAS is consistent with a dysexecutive fronto-subcortical syndrome. However, additional controlled studies are required to progress our understanding of FXTAS and how the neuropsychiatric profile relates to underlying pathological mechanisms.Neuropsychology Review 05/2014; 24(4):491-513. · 6.42 Impact Factor
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ABSTRACT: We recently reported a significant increase in the frequency of carriers of GZ alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ-carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.Clinical Genetics 11/2012; · 4.25 Impact Factor