Zeesman Susan, Zwaigenbaum Lonnie, Whelan Donald T, Hagerman Randi J, Tassone Flora, Taylor Sherryl A M
Department of Pediatrics, McMaster University, Hamilton, Ontario.
Am J Med Genet A. 2004 Aug 30;129A(2):184-9. doi: 10.1002/ajmg.a.30191.
We present a family in which a fragile X mosaic male, who carries both premutation and full mutation alleles in his peripheral blood leukocytes, has a daughter with both premutation and partially methylated full mutation alleles and a significant developmental disability. To our knowledge, this is the first report of such an occurrence and it challenges current thinking about the expansion and transmission of unstable FMR1 alleles from men to their daughters. It is currently accepted that neither males with premutations nor full mutations are at risk for having daughters with full mutations and fragile X syndrome. The sperm cells of full mutation males are thought to carry only premutation alleles. These alleles, when transmitted through a male, regardless of his cognitive status, are thought to be unable to expand to full mutations in the next generation. In effect, the expansion from premutation to full mutation has only been observed through female meioses. The sperm cells in the father in this family have been shown to contain only alleles in the premutation range. Since his daughter has both premutation and full mutation alleles the expansion to full mutation in this case must have occurred postzygotically.
我们报告了一个家族，其中一名外周血白细胞中同时携带前突变和完全突变等位基因的脆性X综合征嵌合男性，育有一个同时携带前突变和部分甲基化完全突变等位基因且患有严重发育障碍的女儿。据我们所知，这是此类情况的首例报告，它挑战了当前关于不稳定FMR1等位基因从男性向其女儿扩展和传递的观点。目前公认，无论是携带前突变的男性还是携带完全突变的男性，其女儿患完全突变和脆性X综合征的风险都不高。完全突变男性的精子细胞被认为只携带前突变等位基因。这些等位基因通过男性传递时，无论其认知状态如何，都被认为无法在下一代中扩展为完全突变。实际上，从前突变到完全突变的扩展仅在女性减数分裂过程中被观察到。该家族中父亲的精子细胞已被证明仅包含前突变范围内的等位基因。由于他的女儿同时拥有前突变和完全突变等位基因，所以在这种情况下向完全突变的扩展一定是在合子形成后发生的。
