中文摘要：

目的探索脆性x综合征（fragile Xsyndrome，FXS）男性生殖系CGG重复不稳定性的发生模式。方法采用AmplideX FMR1 PCR结合Southern印迹对1例FXS全突变男性胎儿和1例全突变与前突变嵌合男性胎儿的睾丸组织进行CGG重复扩增长度及甲基化水平检测，用免疫组化检测睾丸石蜡切片中FMRP的表达。结果PCR产物印迹杂交检测显示，在全突变胎儿睾丸中，除全突变条带外可见较明显的特异前突变条带（CGGl160），而脑组织仅见全突变；嵌合胎儿睾丸与外周血CGG嵌合模式基本相同，未见其他尺寸的前突变条带。全突变胎儿睾丸组织石蜡切片染色可见少数FMRP阳性细胞，表明全突变胎儿睾丸中有FMRP表达。结论通过对两例23周FXS胎儿睾丸组织中CGG数目和FMRP表达的分析，明确了精原细胞22周停止有丝分裂后CGG的重复模式，进一步明确了父源CGG缩减渐进过程，证实FMRP表达与精原细胞增殖过程吻合，推测生殖细胞增殖对FMRP的表达需求是父源cGG重复缩减的诱因。

英文摘要：

Objective To study the pattern of CGG repeat instability within germline cells derived from two male fetuses affected with Fragile X syndrome （FXS）. Methods The length and methylation status of CGG repeats within the testes of a fetus carrying a full FXS mutation and another fetus carrying mosaicism FXS mutation were analyzed with Southern blotting and AmplideX FMR1 PCR. Immunohistochemistry was also applied for the measurement of FMR1 protein （FMRP） expression within the testes. Results For the fetus carrying the full mutation, Southern blotting analysis of the PCR product has detected an expected band representing the full mutation in its brain and a premutation band of 〉 160 CGG repeats in its testis. Whereas the pattern of premutation/full mutation in mosaic testis was similar to that in peripheral blood and no sign of contracted fragment was found other than a band of about 160 CGG repeats. Immunohistochemistry assay with a FMRP-specific antibody demonstrated a number of FMRP- positive germcells, which suggested a contraction from full mutation to premutation alleles. Conclusion This study has clarified the instability pattern of CGG repeat and expression of FMRP protein within the testes of fetuses affected with FXS, confirming that the CGG repeat can contract progressively within the germline. The FMRP expression in the testis is consistent with spermatogonium proliferation, and thus the contraction from full mutation to unmethylated premutations may occur for the requirement of FMRP expression during spermatogenesis. The better understanding of FMRP function during germ cell proliferation may elucidate the mechanism underlying the contraction of full FXS mutation in male germline.