Fu Y H, Kuhl D P, Pizzuti A, Pieretti M, Sutcliffe J S, Richards S, Verkerk A J, Holden J J, Fenwick R G, Warren S T
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
Cell. 1991 Dec 20;67(6):1047-58. doi: 10.1016/0092-8674(91)90283-5.
Fragile X syndrome results from mutations in a (CGG)n repeat found in the coding sequence of the FMR-1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are meiotically unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.
脆性X综合征由FMR-1基因编码序列中（CGG）n重复序列的突变引起。对正常个体该区域长度变异的分析表明，等位基因大小范围从低至6次重复到高至54次重复。在脆性X家族中无表型效应的前突变大小范围为52至200多次重复。所有大于52次重复的等位基因，包括在正常家族中鉴定出的那些，减数分裂不稳定，突变频率为1，而46次重复及以下等位基因的75次减数分裂未显示突变。由于观察到嵌合体现象，前突变等位基因在有丝分裂时也不稳定。卵母细胞发生过程中扩展为与智力迟钝相关的完全突变的风险随重复次数增加，这种风险变化解释了谢尔曼悖论。
