Mazzocco M M
Department of Developmental Cognitive Neurology, Kennedy Krieger Institute; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ment Retard Dev Disabil Res Rev. 2000;6(2):96-106. doi: 10.1002/1098-2779(2000)6:2<96::AID-MRDD3>3.0.CO;2-H.
Fragile X syndrome is a neurodevelopmental disorder that results from a single gene mutation on the X chromosome. The purpose of this review is to summarize key advances made in understanding the fragile X premutation gene seen in carriers and the full mutation gene seen in persons with the syndrome. DNA testing has replaced cytogenetic testing as the primary method for identification of fragile X, although the efficacy of protein level screening is being explored. The premutation is associated with no effects, although there is evidence of physical effects-primarily premature menopause and mild outward features of the fragile X syndrome-among premutation carriers. There is much controversy regarding premutation effects on psychological development. The few experimental studies carried out to date do not suggest noticeable or significant effects. One challenge in addressing this controversy is the sometimes ambiguous differentiation between premutation and full mutation genes. There is a well-established yet highly variable phenotype of the full mutation. Research from this decade has helped to address specific aspects of this phenotype, including the early course of its development in males, the influence of home and family environments, the nature of social difficulties and autistic features seen in boys and girls with fragile X, and the potential role of hyperarousal or hyper-reactivity. Studies in these areas, and on the role of FMR protein, will contribute towards ongoing advances in our understanding of fragile X syndrome and its mechanisms. The variability in physical, social, and cognitive features, as described in this review, is one that prohibits clear-cut screening guidelines designed to avoid high rates of both false positives and false negatives. Results from recent studies indicate the need to consider behavioral features in selecting candidates for fragile X screening. MRDD Research Reviews 2000;6:96-106.
脆性X综合征是一种神经发育障碍，由X染色体上的单个基因突变引起。本综述的目的是总结在理解携带者中所见的脆性X前突变基因和该综合征患者中所见的完全突变基因方面取得的关键进展。DNA检测已取代细胞遗传学检测，成为脆性X鉴定的主要方法，尽管蛋白质水平筛查的功效正在探索中。前突变通常无影响，不过有证据表明前突变携带者存在身体影响——主要是过早绝经和脆性X综合征的轻度外在特征。关于前突变对心理发展的影响存在很多争议。迄今为止进行的少数实验研究并未表明有明显或显著影响。解决这一争议的一个挑战是前突变基因和完全突变基因之间有时难以明确区分。完全突变具有已确定但高度可变的表型。这十年的研究有助于解决该表型的具体方面，包括其在男性中的早期发展过程、家庭环境的影响、脆性X男孩和女孩中出现的社交困难和自闭症特征的性质，以及过度觉醒或反应过度的潜在作用。这些领域的研究以及对FMR蛋白作用的研究，将有助于我们在理解脆性X综合征及其机制方面不断取得进展。如本综述所述，身体、社交和认知特征的变异性使得难以制定明确的筛查指南以避免高比例的假阳性和假阴性。近期研究结果表明，在选择脆性X筛查候选人时需要考虑行为特征。《MRDD研究评论》2000年；6：96 - 106。
