School of Public Health, University of Sydney, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia; Huntington Disease Service, Westmead Hospital, Westmead, NSW, Australia.
Neuroscience Research Australia, Randwick, NSW, Australia; University of New South Wales, Kensington, NSW, Australia.
Lancet. 2014 Mar 1;383(9919):828-40. doi: 10.1016/S0140-6736(13)60630-3. Epub 2013 Aug 6.
25% of all people aged 55 years and older have a family history of dementia. For most, the family history is due to genetically complex disease, where many genetic variations of small effect interact to increase risk of dementia. The lifetime risk of dementia for these families is about 20%, compared with 10% in the general population. A small proportion of families have an autosomal dominant family history of early-onset dementia, which is often due to mendelian disease, caused by a mutation in one of the dementia genes. Each family member has a 50% chance of inheriting the mutation, which confers a lifetime dementia risk of over 95%. In this Review, we focus on the evidence for, and the approach to, genetic testing in Alzheimer's disease (APP, PSEN1, and PSEN2 genes), frontotemporal dementia (MAPT, GRN, C9ORF72, and other genes), and other familial dementias. We conclude by discussing the practical aspects of genetic counselling.
25%的 55 岁及以上老年人有痴呆家族史。对于大多数人来说，家族史是由于遗传复杂疾病所致，其中许多遗传变异的微小影响相互作用会增加痴呆的风险。这些家族的痴呆终身风险约为 20%，而普通人群为 10%。一小部分家族有早发性痴呆的常染色体显性家族史，这通常是由于孟德尔疾病引起的，由一个痴呆基因的突变引起。每个家族成员有 50%的机会遗传突变，这会导致终身痴呆风险超过 95%。在这篇综述中，我们重点讨论了阿尔茨海默病（APP、PSEN1 和 PSEN2 基因）、额颞叶痴呆（MAPT、GRN、C9ORF72 和其他基因）和其他家族性痴呆的遗传检测的证据和方法。最后我们讨论了遗传咨询的实际方面。
