Wolff G, Deuschl G, Wienker T F, Hummel K, Bender K, Lücking C H, Schumacher M, Hammer J, Oepen G
Institut für Humangenetik und Anthropologie, University of Freiburg i Br, Federal Republic of Germany.
J Med Genet. 1989 Jan;26(1):18-27. doi: 10.1136/jmg.26.1.18.
We report a large family with an isolated case of Huntington's disease (HD), which is probably the result of a new mutation. The patient developed clinical signs typical of HD at the age of 36. The clinical course of the patient's disease is documented by several clinical admissions over a period of 14 years at present. The family history is strikingly negative with the parents having been clearly unaffected into their 80s and with 13 older and two younger, living, healthy sibs. Extensive testing of polymorphic markers (blood groups, red cell and serum proteins, HLA antigens) showed no indication of non-paternity, but rather gave strong support to the hypothesis that the proband is a full sib. In addition, DNA typing for several RFLPs known to be closely linked to the HD gene locus indicated that several clearly unaffected sibs share one or the other or both of the patient's haplotypes. This is further evidence in favour of the hypothesis of a new mutation at the HD locus. The posterior probability of a new mutation to HD in the patient exceeds 99%, even if an a priori probability of non-paternity of 10% and a mutation rate of HD of 10(-7) is assumed.
我们报告了一个患有亨廷顿病（HD）孤立病例的大家族，这可能是新突变的结果。该患者在36岁时出现了典型的HD临床症状。目前，在14年的时间里，患者疾病的临床过程通过多次临床入院记录下来。家族史明显呈阴性，其父母在80多岁时显然未受影响，还有13个年龄较大和2个年龄较小的在世健康兄弟姐妹。对多态性标记（血型、红细胞和血清蛋白、HLA抗原）的广泛检测未显示非父系迹象，反而有力支持了先证者是同胞手足的假设。此外，对几个已知与HD基因位点紧密连锁的限制性片段长度多态性（RFLP）进行DNA分型表明，几个明显未受影响的兄弟姐妹共享患者的一种或另一种或两种单倍型。这进一步证明了HD位点发生新突变的假设。即使假定非父系的先验概率为10%且HD的突变率为10^(-7)，该患者发生HD新突变的后验概率仍超过99%。
