van Oost B A, Smits A P, Dreesen J C, van den Ouweland A M, Oostra B A
Department of Human Genetics, Erasmus University, Rotterdam, The Netherlands.
Am J Med Genet. 1992;43(1-2):320-7. doi: 10.1002/ajmg.1320430149.
We have evaluated our carrier testing for the fragile X [fra(X)] syndrome, which was based on linked DNA markers, with the direct analysis of the CGG repeat sequence in the fra(X) gene. PstI and EcoRI blots were hybridized with a probe derived from the region just 3' of the CGG repeat in Xq27.3. We found the mutation analysis to be very sensitive as all 71 obligate gene carriers as well as 135 fra(X) patients tested showed evidence for an increased restriction fragment length encompassing the CGG repeat sequence with or without dispersion of the hybridization signal (mosaicism). Based on linked DNA markers, 6 out of 50 cytogenetic negative and mentally normal males at risk and 15 of 72 females at risk had inherited the allele at risk. All of these diagnoses could be confirmed by analysis of the CGG repeat length.
我们评估了基于连锁DNA标记的脆性X综合征（fra(X)）携带者检测方法，并对fra(X)基因中的CGG重复序列进行了直接分析。用位于Xq27.3中CGG重复序列3'端区域的探针与PstI和EcoRI印迹杂交。我们发现突变分析非常灵敏，因为所检测的71名确定的基因携带者以及135名fra(X)患者均显示出包含CGG重复序列的限制性片段长度增加，无论杂交信号是否分散（嵌合体）。基于连锁DNA标记，50名细胞遗传学检测阴性且有患病风险的智力正常男性中有6名，72名有患病风险的女性中有15名遗传了有风险的等位基因。所有这些诊断结果均可通过分析CGG重复长度得到证实。
