Crawford D C, Acuña J M, Sherman S L
Centers for Disease Control and Prevention, Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Atlanta, Georgia, USA.
Genet Med. 2001 Sep-Oct;3(5):359-71. doi: 10.1097/00125817-200109000-00006.
The fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is one of the most common forms of inherited mental retardation. The cognitive, behavioral, and physical phenotype varies by sex, with males being more severely affected because of the X-linked inheritance of the mutation. The disorder-causing mutation is the amplification of a CGG repeat in the 5' untranslated region of FMR1 located at Xq27.3. The fragile X CGG repeat has four forms: common (6-40 repeats), intermediate (41-60 repeats), premutation (61-200 repeats), and full mutation (>200-230 repeats). Population-based studies suggest that the prevalence of the full mutation, the disorder-causing form of the repeat, ranges from 1/3,717 to 1/8,918 Caucasian males in the general population. The full mutation is also found in other racial/ethnic populations; however, few population-based studies exist for these populations. No population-based studies exist for the full mutation in a general female population. In contrast, several large, population-based studies exist for the premutation or carrier form of the disorder, with prevalence estimates ranging from 1/246 to 1/468 Caucasian females in the general population. For Caucasian males, the prevalence of the premutation is approximately 1/1,000. Like the full mutation, little information exists for the premutation in other populations. Although no effective cure or treatment exists for the fragile X syndrome, all persons affected with the syndrome are eligible for early intervention services. The relatively high prevalence of the premutation and full mutation genotypes coupled with technological advances in genetic testing make the fragile X syndrome amenable to screening. The timing as well as benefits and harms associated with the different screening strategies are the subject of current research and discussion.
脆性X综合征是一种外显率降低的X连锁显性疾病，是遗传性智力迟钝最常见的形式之一。认知、行为和身体表型因性别而异，由于突变的X连锁遗传，男性受影响更严重。致病突变是位于Xq27.3的FMR1基因5'非翻译区CGG重复序列的扩增。脆性X CGG重复序列有四种形式：常见型（6 - 40次重复）、中间型（41 - 60次重复）、前突变型（61 - 200次重复）和全突变型（>200 - 230次重复）。基于人群的研究表明，全突变型（即导致该疾病的重复序列形式）在普通人群中白种男性中的患病率为1/3717至1/8918。全突变型在其他种族/族裔人群中也有发现；然而，针对这些人群的基于人群的研究很少。目前尚无关于普通女性人群中全突变型的基于人群的研究。相比之下，针对该疾病前突变型或携带者形式有几项大型的基于人群的研究，普通人群中白种女性的患病率估计为1/246至1/468。对于白种男性，前突变型的患病率约为1/1000。与全突变型一样，关于其他人群前突变型的信息也很少。尽管目前尚无针对脆性X综合征的有效治愈方法或治疗手段，但所有受该综合征影响的人都有资格获得早期干预服务。前突变型和全突变型基因型的相对高患病率以及基因检测技术的进步使得脆性X综合征适合进行筛查。不同筛查策略的时机以及相关的益处和危害是当前研究和讨论的主题。
