From the Center for Medical Genetics and Molecular Medicine (G.H., O.B.), Haukeland University Hospital, Bergen; Section for Medical Genetics (I.B.), Department of Pathology, St. Olavs Hospital, Trondheim, Norway; Centre for Molecular Medicine and Therapeutics (M.R.H., A.S.), Vancouver; and University of British Columbia (M.R.H., A.S.), Vancouver, Canada.
Neurology. 2013 Sep 17;81(12):1099-100. doi: 10.1212/WNL.0b013e3182a4a4af. Epub 2013 Aug 14.
Huntington disease (HD, OMIM #143100) is a dominantly inherited neurodegenerative disorder due to a CAG repeat expansion in the gene, encoding a polyglutamine tract in the N-terminal part of the huntingtin protein. Most cases are inherited from an affected parent, but in about 10% of cases the condition appears to be de novo. De novo or sporadic cases are usually due to CAG repeat expansion of intermediate alleles. Intermediate alleles have 27–35 CAG repeats, and the higher the number of repeats, the higher the risk for expansion into disease range, usually upon paternal transmission. In most cases, the change in repeat size is minor, and gradual increases into the disease range over several generations is the basis of new genetic mutations and stable disease prevalence. So far, the largest single-step expansions reported were from 27 to 38 and from 35 to 58 CAG repeats. It has recently been shown that intermediate alleles and disease alleles share the same haplotypes, which is expected if intermediate alleles are the main source of new mutation cases. The high-risk haplotypes are called A1 and A2, and are both prevalent among Caucasians but rare in other ethnic groups.
亨廷顿病（HD，OMIM #143100）是一种显性遗传性神经退行性疾病，由 基因中的 CAG 重复扩展引起，该基因编码亨廷顿蛋白 N 端部分的多聚谷氨酰胺片段。大多数病例是由受影响的父母遗传的，但在大约 10%的病例中，这种情况似乎是从头发生的。从头发生或散发性病例通常是由于中间等位基因的 CAG 重复扩展。中间等位基因有 27-35 个 CAG 重复，重复次数越高，扩展到疾病范围的风险就越高，通常是通过父系传递。在大多数情况下，重复大小的变化很小，在几代人的时间里逐渐增加到疾病范围是新基因突变和稳定疾病流行的基础。到目前为止，报道的最大单一扩展是从 27 到 38 和从 35 到 58 CAG 重复。最近表明，中间等位基因和疾病等位基因共享相同的单倍型，如果中间等位基因是新突变病例的主要来源，这是可以预期的。高风险单倍型称为 A1 和 A2，它们在白种人中都很常见，但在其他种族中很少见。
