脆性 X 综合征是一最常见的 X 性连锁的遗传性智力低下病,是因 X 染色体上脆性部位的FMR—1基因内一段不稳定的 CGG 重复序列的异常扩增所致。本文建立了多聚酶链反应—变性梯度聚丙烯酰胺凝胶电泳(PCR—DGGE)方法,并成功地检测出83例...脆性 X 综合征是一最常见的 X 性连锁的遗传性智力低下病,是因 X 染色体上脆性部位的FMR—1基因内一段不稳定的 CGG 重复序列的异常扩增所致。本文建立了多聚酶链反应—变性梯度聚丙烯酰胺凝胶电泳(PCR—DGGE)方法,并成功地检测出83例正常人 X 染色体脆性位点FMR—1基因内 CGG 重复序列片段。在上述83例正常人中发现有16个不同大小的等位基因,说明该重复序列的长度在中国人中具有丰富的多态性,最常见的等位基因大小为308bP,有29个CGG 重复。文章对 PCR 方法扩增该 CGG 重复序列片段成功的关键如在反应体系中加入 dGTP 类似物7—deaza—dGTP,DMSO 以及它们在反应体系中理想的浓度等进行了详细的讨论。由于该方法能显示800bP 以内的 DNA 片段,并能准确确定 FMR—1基因内 CGG 重复序列的 CGG 重复数.在用于脆性 X 综合征的女性携带者检出时特别有意义,可根据 CGG 重复数估计其后代受累的风险率及受累程度。该方法稳定可靠,简便宜行,适合推广应用于脆性 X 综合征患者及携带者的临床诊断和遗传咨询及筛查。展开更多
AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chrom...AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability(ID). In this previous study,87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples(162 females and 283 males).RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527(1.7%). The prevalence in males and females is 1.5%(5/329) and 2%(4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited.CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.展开更多
文摘脆性 X 综合征是一最常见的 X 性连锁的遗传性智力低下病,是因 X 染色体上脆性部位的FMR—1基因内一段不稳定的 CGG 重复序列的异常扩增所致。本文建立了多聚酶链反应—变性梯度聚丙烯酰胺凝胶电泳(PCR—DGGE)方法,并成功地检测出83例正常人 X 染色体脆性位点FMR—1基因内 CGG 重复序列片段。在上述83例正常人中发现有16个不同大小的等位基因,说明该重复序列的长度在中国人中具有丰富的多态性,最常见的等位基因大小为308bP,有29个CGG 重复。文章对 PCR 方法扩增该 CGG 重复序列片段成功的关键如在反应体系中加入 dGTP 类似物7—deaza—dGTP,DMSO 以及它们在反应体系中理想的浓度等进行了详细的讨论。由于该方法能显示800bP 以内的 DNA 片段,并能准确确定 FMR—1基因内 CGG 重复序列的 CGG 重复数.在用于脆性 X 综合征的女性携带者检出时特别有意义,可根据 CGG 重复数估计其后代受累的风险率及受累程度。该方法稳定可靠,简便宜行,适合推广应用于脆性 X 综合征患者及携带者的临床诊断和遗传咨询及筛查。
基金Risbin-Iptekdok 2007/2008,Ministry of Health Republic of IndonesiaExcellent Scholarship(Beasiswa Unggulan Program),Foreign Scholarship(Beasiswa Luar Negeri),Directorate of Higher Education(DGHE)+1 种基金Ministry of National Education Republic of Indonesiathe PhD-fellowship Program of the Radboud University(RU-fellowship)
文摘AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability(ID). In this previous study,87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples(162 females and 283 males).RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527(1.7%). The prevalence in males and females is 1.5%(5/329) and 2%(4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited.CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.
