Smits A P, Dreesen J C, Post J G, Smeets D F, de Die-Smulders C, Spaans-van der Bijl T, Govaerts L C, Warren S T, Oostra B A, van Oost B A
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
J Med Genet. 1993 Feb;30(2):94-6. doi: 10.1136/jmg.30.2.94.
Fragile X (fra(X)) syndrome, the most common form of familial mental retardation, is caused by heritable unstable DNA composed of CGG repeats. As reproductive fitness of fra(X) patients is severely compromised, a high mutation rate has been proposed to explain the high prevalence. However, we have been unable to show any new mutation for 84 probands referred to us to date. We show here the same fra(X) gene in five fra(X) probands with common ancestors married in 1747. The lack of new fra(X) mutations implies that there must be many more fra(X) gene carriers in the population than previously realised. As it is now possible to detect asymptomatic fra(X) gene carriers by DNA analysis, extended family studies for any new proband are recommended. A family illustrating the importance of fra(X) carriership determination is reported.
脆性X综合征（fra(X)）是家族性智力迟钝最常见的形式，由由CGG重复序列组成的可遗传不稳定DNA引起。由于fra(X)患者的生殖适应性严重受损，有人提出高突变率来解释其高患病率。然而，迄今为止，我们尚未在转介给我们的84名先证者中发现任何新的突变。我们在此展示了1747年结婚的有共同祖先的五名fra(X)先证者中相同的fra(X)基因。缺乏新的fra(X)突变意味着人群中fra(X)基因携带者的数量肯定比以前意识到的要多得多。由于现在可以通过DNA分析检测无症状的fra(X)基因携带者，建议对任何新的先证者进行扩展的家系研究。本文报道了一个说明确定fra(X)携带者重要性的家系。
