Brown W T, Gross A, Goonewardena P, Ferrando C, Dobkin C, Jenkins E C
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, N.Y. 11030.
Am J Med Genet. 1991 Feb-Mar;38(2-3):292-7. doi: 10.1002/ajmg.1320380226.
Segregation analysis of the fragile-X [fra(X)] syndrome uncovered an unexpected 20% excess of normal males among sibships by Sherman et al. (Sherman SL, Morton NE, Jacobs PA, Turner G [1984]. Ann Hum Genet 48:21-37; Sherman SL, Jacobs PA, Morton NE, Froster-Iskenius U, Howard-Peebles PN, Neilsen KB, Partington MW, Sutherland GR, Turner G, Watson M [1985]: Hum Genet 63:289-299). This result predicts that about 17% (1/6) of normal sons of carrier fra(X) females will be non-penetrant. A way to test this prediction is by DNA markers. We analyzed DNA samples from 100 families with a set of flanking DNA markers linked to the fra(X) locus. Ten of 51 (19.6%) normal brothers, doubly informative and non-recombinant for flanking DNA markers, were found to be non-penetrant males. This result closely confirms the predictions of the segregation analysis indicating that about 1/6 of normal brothers are non-penetrant carrier males. The use of DNA markers to identify non-penetrant brothers and grandfathers can help to clarify the inheritance of the fra(X) mutation and be of considerable clinical usefulness. Using DNA markers, it was possible to study grandparental transmission in 71 of the families. In 39 families, DNA analysis confirmed the apparent pattern of inheritance. In 18 families, the grandparents had a single daughter with affected children. Of these, a new mutation at the time of their daughters' conception was possible in 15 and quite likely in 3. In 14 families with 2 or more daughters with affected fra(X) offspring, the grandparents had no affected sons or other relatives known to be positive for fra(X).(ABSTRACT TRUNCATED AT 250 WORDS)
谢尔曼等人对脆性X [fra(X)] 综合征进行的分离分析发现，同胞亲属中正常男性意外地多出20%（谢尔曼SL、莫顿NE、雅各布斯PA、特纳G [1984年]。《人类遗传学杂志》48:21 - 37；谢尔曼SL、雅各布斯PA、莫顿NE、弗罗斯特 - 伊斯克纽斯U、霍华德 - 皮布尔斯PN、尼尔森KB、帕廷顿MW、萨瑟兰GR、特纳G、沃森M [1985年]：《人类遗传学》63:289 - 299）。这一结果预测，携带fra(X)的女性所生正常儿子中约17%（1/6）将为非外显者。检验这一预测的一种方法是使用DNA标记。我们用一组与fra(X)位点连锁的侧翼DNA标记分析了100个家庭的DNA样本。在51名正常兄弟中，有10名（19.6%）对于侧翼DNA标记具有双重信息且非重组，被发现是非外显男性。这一结果紧密证实了分离分析的预测，表明约1/6的正常兄弟是非外显携带者男性。使用DNA标记来识别非外显兄弟和祖父有助于阐明fra(X)突变的遗传方式，具有相当大的临床实用性。利用DNA标记，有可能在71个家庭中研究祖父母的遗传传递情况。在39个家庭中，DNA分析证实了明显的遗传模式。在18个家庭中，祖父母有一个女儿，其子女患病。其中，在15个家庭中其女儿受孕时可能发生了新的突变，在3个家庭中很可能发生了新的突变。在14个有两个或更多女儿且其子女患有fra(X)的家庭中，祖父母没有患病的儿子或其他已知携带fra(X)阳性的亲属。（摘要截取自250词）
