Hoegerman S F, Rary J M
Am J Med Genet. 1986 Jan-Feb;23(1-2):685-99. doi: 10.1002/ajmg.1320230160.
We suggest that mutations for fragile X-positive Martin-Bell syndrome, and perhaps also for achondroplasia, may result from the insertion of transposable elements (TE's). Loss of genetic function could result from either the insertion of TE's within or adjacent to a normal chromosomal gene or, in the case of fragile X, from the loss of genes distal to the site of TE insertion following subsequent TE excision without ligation of the resulting discontinuity. The phenotypically and often cytogenetically normal transmitting males in fragile X pedigrees are interpreted not as "nonpenetrant" transmitters of a fully formed fragile X but rather as transmitters of some or all of the factors necessary for TE insertion at Xq27. We consider it likely that such insertion frequently first occurs, both in soma and especially in the germline, in their daughters. Our models predict that father to son transmission of causative factors would be a common occurrence in fragile X pedigrees. The absence of documented father to son transmission either points to a flaw in the models or reflects systematic bias in the collection of pedigree information.
我们认为，脆性X阳性马丁-贝尔综合征的突变，或许还有软骨发育不全的突变，可能是转座元件（TE）插入所致。基因功能的丧失可能源于TE插入正常染色体基因内部或其邻近区域，或者就脆性X而言，是由于随后TE切除后未连接所产生的断点，导致TE插入位点远端基因的丢失。脆性X家系中表型通常正常且细胞遗传学上也正常的传递男性，不应被视为完全形成的脆性X的“非外显”传递者，而应被视为在Xq27处插入TE所需的部分或全部因子的传递者。我们认为这种插入很可能首先在体细胞中，尤其是在生殖细胞中，频繁地发生在他们的女儿身上。我们的模型预测，致病因子在脆性X家系中从父亲传给儿子将是常见现象。缺乏记录在案的从父亲到儿子的传递，要么表明模型存在缺陷，要么反映了家系信息收集过程中的系统性偏差。
