Sherman S L, Maddalena A, Howard-Peebles P N, Brown W T, Nolin S, Jenkins E, Schwartz C, Tarrelton J, Shapiro L R, Smits A P
Department of Genetics and Molecular Medicine, Emory University, Atlanta, Georgia 30322.
Am J Med Genet. 1994 Jul 15;51(4):503-6. doi: 10.1002/ajmg.1320510442.
The Prospective Study of the Fragile X Syndrome is a large collaborative effort designed to collect prospective data on the pregnancy outcomes of individuals who carry the fragile X mutation. The goal of this 5-year study is to obtain empiric recurrence risks and population parameters for the fragile X syndrome in order to characterize the underlying mechanism of the mutation and the factors that influence its expression. This report presents the DNA results on the first 152 cases of female carriers and their pregnancy outcomes. It was found that the sex ratio of conceptuses was not significantly different from 1.0 and was not associated with mutation status. Thus, there was no evidence for selection against zygotes with full mutations. There was a significant association between the form of the mutation in carrier mothers and the frequency of its transmission. Examination of the segregation ratios from premutation mothers showed that there was a deficit of conceptuses that received the fragile X mutation. The segregation ratio from full mutation carrier mothers did not differ from expected. Several explanations for this observation are discussed. Numbers of cases are too small to estimate recurrence risks; however, the general trend of the data confirm the association of recurrence risks and the repeat number carried by the mother.
脆性X综合征前瞻性研究是一项大规模合作项目，旨在收集携带脆性X突变个体的妊娠结局前瞻性数据。这项为期5年的研究目标是获取脆性X综合征的经验性复发风险和群体参数，以描述该突变的潜在机制以及影响其表达的因素。本报告展示了首批152例女性携带者的DNA检测结果及其妊娠结局。研究发现，胎儿的性别比与1.0无显著差异，且与突变状态无关。因此，没有证据表明存在针对完全突变合子的选择。携带者母亲的突变形式与其传递频率之间存在显著关联。对前突变母亲的分离比进行检查发现，接受脆性X突变的胎儿数量不足。完全突变携带者母亲的分离比与预期无差异。本文讨论了对此观察结果的几种解释。由于病例数量过少，无法估计复发风险；然而，数据的总体趋势证实了复发风险与母亲携带的重复序列数量之间的关联。
