Smits A, Smeets D, Hamel B, Dreesen J, van Oost B
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
Am J Med Genet. 1992;43(1-2):345-52. doi: 10.1002/ajmg.1320430153.
The overall prevalence of the fragile X [fra(X)] mutation, as determined by population studies, is approximately 1 in 850 [Gustavson et al., 1986; Webb et al., 1986]. This prevalence suggests a very high mutation rate which, in turn, suggests that many patients have to represent sporadic cases. In order to obtain an accurate estimate of the proportion of sporadic cases, we performed genealogic, cytogenetic and DNA linkage studies as well as direct analysis of the CGG repeat in relatives of 84 fra(X) probands. We did not find any evidence for the presence of sporadic cases. In 11 probands consanguinity could be proven by the detection of common ancestors, in 5 related families up to 9 generations ago. In the other 6 related families the mutation could be traced back 4-6 generations. In 3 or more generation families we were able to demonstrate that half of the probands carried the grandpaternal fra(X) gene. These results imply that rather than a high mutation rate, both Normal Transmitting Males (NTM's) and mentally normal female carriers contribute considerably to the high prevalence of the fra(X) syndrome.
根据群体研究确定，脆性X [fra(X)] 突变的总体患病率约为1/850 [古斯塔夫森等人，1986年；韦伯等人，1986年]。这种患病率表明突变率非常高，这反过来又表明许多患者必定代表散发病例。为了准确估计散发病例的比例，我们对84名fra(X) 先证者的亲属进行了系谱、细胞遗传学和DNA连锁研究，以及对CGG重复序列的直接分析。我们没有发现任何散发病例存在的证据。在11名先证者中，通过检测共同祖先证实存在近亲结婚，最远追溯到9代以前的5个相关家族。在其他6个相关家族中，突变可追溯到4 - 6代。在三代或三代以上的家族中，我们能够证明一半的先证者携带祖父的fra(X) 基因。这些结果表明，脆性X综合征的高患病率并非由高突变率所致，正常传递男性（NTM）和智力正常的女性携带者都对其有显著影响。
