Ridley R M, Farrer L A, Frith C D, Conneally P M
Division of Psychiatry, Clinical Research Centre, Harrow, Middlesex.
Am J Hum Genet. 1992 Mar;50(3):536-43.
Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring was not compatible with this hypothesis. Furthermore, neither the excess of affected grandfathers nor the existence of juvenile-onset and adult-onset cases within a sibship would be predicted by this model. We also rejected a more general hypothesis that a major change in gene expression across generations, measured by the presence of juvenile onset and/or major anticipation, is determined by an X-linked modifier. However, the inheritance of a propensity toward juvenile onset via the affected male line could be due to an abnormal pattern of paternal genomic imprinting.
亨廷顿病的青少年发病由患病亲本中的一个X连锁隐性修饰基因决定。有此类后代的患病父亲与患病母亲的观察比例与该假说不相符。此外，该模型无法预测患病祖父的过量情况，也无法预测同胞中青少年发病和成人发病病例的存在。我们还否决了一个更普遍的假说，即通过青少年发病和/或主要的遗传早现来衡量的跨代基因表达的重大变化由一个X连锁修饰基因决定。然而，经由患病男性系谱遗传的青少年发病倾向可能归因于父本基因组印记的异常模式。
