Kraff Jeremy, Tang Hiu-Tung, Cilia Roberto, Canesi Margherita, Pezzoli Gianni, Goldwurm Stefano, Hagerman Paul J, Tassone Flora
Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, One Shields Avenue, Davis, CA 95616, USA.
Arch Neurol. 2007 Jul;64(7):1002-6. doi: 10.1001/archneur.64.7.1002.
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.
To screen DNA samples (male) from an Italian Parkinson disease clinic for an excess of premutation expansions of the FMR1 gene.
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.
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.
A cohort of unrelated males with clinical features of parkinsonism. All but 12 males were of Italian origin, and all reported Caucasian ethnicity.
CGG repeat number.
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.
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.
脆性X相关震颤/共济失调综合征患者常伴有帕金森病特征，常导致最初被诊断为帕金森病或其他帕金森病谱系障碍。因此，帕金森病患者群体可能包括携带脆性X智力低下1（FMR1）基因前突变扩展（55 - 200个CGG重复序列）的个体。
对一家意大利帕金森病诊所的男性DNA样本进行筛查，以检测FMR1基因前突变扩展的情况。
通过连续门诊从903名无血缘关系的男性中获取DNA样本，采用增强聚合酶链反应方法分析以检测扩展的CGG重复序列。
诊断评估在意大利米兰的帕金森研究所（Istituti Clinici di Perfezionamento）进行。基因分型在加利福尼亚大学戴维斯分校医学院进行。
一组具有帕金森病临床特征的无血缘关系男性。除12名男性外均为意大利裔，所有参与者均报告为白种人。
CGG重复数。
鉴定出3名前突变携带者（CGG重复数分别为61、69和80）（0.33%），这并不显著高于一般人群中前突变等位基因的频率。本研究是迄今为止对帕金森病患者进行的最大规模筛查，其结果支持了之前对较小帕金森病队列的筛查。
在没有提示FMR1基因受累的额外临床或家族史数据的情况下，对帕金森病患者群体进行前突变等位基因的广泛筛查不太可能有成效。
