Brackenridge C J, Teltscher B
J Med Genet. 1975 Mar;12(1):64-9. doi: 10.1136/jmg.12.1.64.
In an attempt to relate the age at onset of Huntington's disease to parental factors, the effects of parental onset-age (Po) and the age of the transmitting parent at the birth of a subsequently affected child (Pc) have been examined in a sample of cases ascertained from Victorian kindreds. There was a significant positive linear regression of onset-age on the variable Po-Pc; the result was independent of the sex of affected parent or child. It is suggested that the pathogenetic process is activated in individuals at a fixed time before their genetically determined onset-ages and need not commence at birth. Somatic gene mutations accumulating with age may interact with modifiers activated at initiation of pathogenesis and favour the transmission of genes determining early onset. An important conclusion for genetic counselling is the desirability of parents at risk who intend to have children to plan their families early in life so that the illness will tend to appear in late adulthood in their affected children. The regression equation may also be applied to estimate the risk of inheritance of the disorder and, by taking interfamilial variation into account, appears to have an advantage over the esisting method based on the distribution of onsettages.
为了探究亨廷顿舞蹈症的发病年龄与父母因素之间的关系，我们在一组来自维多利亚家族的病例样本中，研究了父母的发病年龄（Po）以及受影响子女出生时传递基因的父母的年龄（Pc）的影响。发病年龄与变量Po - Pc之间存在显著的正线性回归；该结果与受影响的父母或子女的性别无关。研究表明，致病过程在个体达到其基因决定的发病年龄之前的某个固定时间被激活，不一定在出生时就开始。随着年龄积累的体细胞基因突变可能与发病初期激活的修饰因子相互作用，并有利于决定早发的基因的传递。对于遗传咨询而言，一个重要的结论是，有风险的父母若打算生育，应在年轻时尽早规划家庭，以便疾病倾向于在其受影响子女的成年后期出现。回归方程也可用于估计该疾病的遗传风险，并且通过考虑家族间的差异，似乎比基于发病年龄分布的现有方法更具优势。
