Hull C, Hagerman R J
Child Development Unit, Children's Hospital, Denver, CO 80218.
Am J Dis Child. 1993 Nov;147(11):1236-41. doi: 10.1001/archpedi.1993.02160350110017.
The physical features of fragile X, including a long face, prominent ears, and hyperextensible joints, are present in affected males and females. Cytogenetically negative heterozygotes have been considered to be unaffected by the fragile X mental retardation-1 (FMR-1) gene. This study investigated the penetrance of the FMR-1 gene in cytogenetically negative but DNA-positive heterozygotes with a premutation (cytosine guanine guanine [CGG] amplification in the 50 to 200 repeat range), compared with carriers with a full mutation (> 200 CGG repeats) and control subjects. One hundred thirty-nine women with normal IQs between the ages of 18 and 45 years were studied. All underwent cytogenetic and DNA testing to determine their fragile X carrier status. A medical history-taking and a physical examination, including selected anthropometric measurements, were performed. Results indicate that the FMR-1 mutation mildly affects the physical phenotype of individuals even in the premutation state, although less dramatically than more affected heterozygotes. Carriers with a premutation differed significantly from control subjects in overall physical index score and in the anthropometric measure of ear prominence. These results suggest a phenotypic impact of the FMR-1 mutation even at the 50 to 200 CGG repeat length.
脆性X综合征的身体特征，包括长脸、大耳朵和关节过度伸展，在受影响的男性和女性中都有表现。细胞遗传学检测呈阴性的杂合子曾被认为不受脆性X智力低下1（FMR - 1）基因影响。本研究调查了FMR - 1基因在细胞遗传学检测呈阴性但DNA检测呈阳性的前突变杂合子（50至200次重复范围内的胞嘧啶 - 鸟嘌呤 - 鸟嘌呤[CGG]扩增）中的外显率，并与完全突变（> 200次CGG重复）携带者和对照受试者进行比较。对139名年龄在18至45岁之间、智商正常的女性进行了研究。所有受试者都接受了细胞遗传学和DNA检测以确定其脆性X携带者状态。进行了病史采集和体格检查，包括选定的人体测量。结果表明，即使处于前突变状态，FMR - 1突变也会对个体的身体表型产生轻微影响，尽管程度不如受影响更严重的杂合子明显。前突变携带者在总体身体指数评分和耳朵突出度的人体测量方面与对照受试者有显著差异。这些结果表明，即使在CGG重复长度为50至200时，FMR - 1突变也会对表型产生影响。
