Smits A, Smeets D, Dreesen J, Hamel B, de Haan A, van Oost B
Department of Human Genetics, University Hospital, Nijmegen, The Netherlands.
Am J Med Genet. 1992;43(1-2):261-7. doi: 10.1002/ajmg.1320430141.
The fragile X [fra(X)] syndrome is the most frequent form of inherited mental retardation, and co-segregates with a fragile site at Xq27.3 as well as with insertion of a variable number of trinucleotide repeats in the 5'-end of the FMR-1 gene. As the fra(X) gene is transmitted by females as well as males, we have investigated whether the parental origin of the fra(X) gene has an effect upon the cytogenetic expression and CGG repeat length. An increased fragment length of 0.2-0.6 kb appeared to be associated with a very low expression or even complete absence of the fragile site as well as with a normal phenotype, and was seen mostly in cases of paternal inheritance. However, in most female carriers with the maternally inherited fra(X) gene we found dispersed fragments ranging from 1.4-6.5 kb or even complete absence of a hybridization signal. Within the group of female carriers with the maternally inherited fra(X) gene we found a statistically significant correlation between the level of the cytogenetic expression and the PstI restriction fragment length encompassing the CGG repeat. These data can be taken as indirect evidence that CGG repeat length and cytogenetic expression are causally related.
脆性X [fra(X)] 综合征是遗传性智力迟钝最常见的形式，它与Xq27.3处的一个脆性位点以及FMR-1基因5'端可变数量的三核苷酸重复序列的插入共同分离。由于fra(X)基因可由女性和男性传递，我们研究了fra(X)基因的亲本来源是否对细胞遗传学表达和CGG重复长度有影响。0.2 - 0.6 kb的片段长度增加似乎与脆性位点的极低表达甚至完全缺失以及正常表型相关，并且大多见于父系遗传的病例中。然而，在大多数携带母系遗传的fra(X)基因的女性携带者中，我们发现片段分散在1.4 - 6.5 kb之间，甚至完全没有杂交信号。在携带母系遗传的fra(X)基因的女性携带者群体中，我们发现细胞遗传学表达水平与包含CGG重复序列的PstI限制性片段长度之间存在统计学上的显著相关性。这些数据可作为CGG重复长度与细胞遗传学表达存在因果关系的间接证据。
