Alford R L, Ashizawa T, Jankovic J, Caskey C T, Richards C S
Baylor DNA Diagnostic Laboratory, Baylor College of Medicine, Houston, TX 77030, USA.
Am J Med Genet. 1996 Dec 18;66(3):281-6. doi: 10.1002/(SICI)1096-8628(19961218)66:3<281::AID-AJMG9>3.0.CO;2-S.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expansion of a variable length (CAG)n repeat in the 5' coding region of a novel gene on chromosome 4p16.3. We provide comprehensive molecular analysis of a sporadic case of HD in which a paternally derived normal length allele expanded to an affected length allele. Linkage analysis and paternity testing confirm the paternal origin of the expansion and demonstrate that unequal crossing over during meiosis is an unlikely mechanism for de novo expansion in HD. This case identifies a complex genetic counseling issue for the families of sporadic cases since calculations of recurrence risk are not possible at this time. In addition, we describe utilization of a combination of polymerase chain reaction (PCR) based assays for examination of both the CAG repeat and an adjacent variable length CCG repeat in the huntingtin gene. The combination of these assays can increase the accuracy of molecular diagnosis for HD and may clarify any ambiguous results obtained during molecular testing of HD families.
亨廷顿舞蹈症（HD）是一种常染色体显性神经退行性疾病，由位于4号染色体p16.3区域的一个新基因5'编码区可变长度（CAG）n重复序列的扩增引起。我们对一例散发型HD病例进行了全面的分子分析，其中一个来自父亲的正常长度等位基因扩展为一个受影响长度的等位基因。连锁分析和亲子鉴定证实了该扩增的父系起源，并表明减数分裂期间不等交换不太可能是HD中从头扩增的机制。该病例为散发病例的家庭识别出一个复杂的遗传咨询问题，因为目前无法计算复发风险。此外，我们描述了利用基于聚合酶链反应（PCR）的检测组合来检测亨廷顿基因中的CAG重复序列和相邻的可变长度CCG重复序列。这些检测方法的组合可以提高HD分子诊断的准确性，并可能澄清HD家系分子检测过程中获得的任何模糊结果。
