Semaka A, Hayden M R
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
Clin Genet. 2014 Apr;85(4):303-11. doi: 10.1111/cge.12324. Epub 2014 Jan 15.
Intermediate alleles (IAs) for Huntington disease (HD) contain 27-35 CAG repeats, a range that falls just below the disease threshold of 36 repeats. While there is no firm evidence that IAs confer the HD phenotype, they are prone to germline CAG repeat instability, particularly repeat expansion when paternally transmitted. Consequently, offspring may inherit a new mutation and develop the disease later in life. Over the last 5 years there has been a renewed interest in IAs. This article provides an overview of the latest research on IAs, including their clinical implications, frequency, haplotype, and likelihood of CAG repeat expansion, as well as patient understanding and current genetic counselling practices. The implications of this growing evidence base for clinical practice are also highlighted. These evidence-based genetic counselling implications may help ensure individuals with an IA predictive test result receive appropriate support, education, and counselling.
亨廷顿舞蹈病(HD)的中间等位基因(IA)含有27 - 35个CAG重复序列,这一范围刚好低于36个重复序列的疾病阈值。虽然没有确凿证据表明IA会导致HD表型,但它们易于发生生殖系CAG重复序列不稳定,尤其是父系传递时的重复序列扩增。因此,后代可能会继承一个新的突变,并在以后的生活中发病。在过去5年里,人们对IA重新产生了兴趣。本文概述了关于IA的最新研究,包括它们的临床意义、频率、单倍型以及CAG重复序列扩增的可能性,还有患者的理解情况和当前的遗传咨询实践。还强调了这一不断增长的证据基础对临床实践的影响。这些基于证据的遗传咨询意义可能有助于确保IA预测检测结果呈阳性的个体获得适当的支持、教育和咨询。