Nacmias B, Piaceri I, Bagnoli S, Tedde A, Piacentini S, Sorbi S
Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Neuroscience, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Curr Mol Med. 2014;14(8):993-1000. doi: 10.2174/1566524014666141010152143.
The genetics of neurodegenerative diseases has an important role to clarify the pathogenetic mechanism, the diagnosis and finally the therapeutic and ethical implications. Moreover, the genetic approach to the study of the main clinical forms of dementia (Alzheimer's disease-AD and Frontotemporal Dementia-FTD) suggests clinical guidelines for helping families to navigate through these complexities. AD and FTD are multifactorial, genetically complex diseases involving many candidate genes. Mutations in three genes (i.e. Amyloid Precursor Protein, APP; presenilin 1, PSEN1; presenilin 2, PSEN2) have been linked to 50% of all familial forms of AD (FAD). Genome wide association studies (GWAS) have involved an increasing number of genes with a possible role in the disease pathogenesis. Up to now, the genetics of familial forms of FTD is related to 7 genes: the microtubule-associated protein tau (MAPT) progranulin (GRN), the valosin-containing protein (VCP), chromatin-modifying 2B (CHMP2B), the TARDNA binding protein 43 encoding gene (TARBDP), fused in sarcoma (FUS) and the last hexanucleotide expansion repeats in the open reading frame of chromosome 9 (C9orf72). Pre-test counseling and the identification of genetic defects are important in both patients and asymptomatic at risk family members.
神经退行性疾病的遗传学对于阐明发病机制、诊断以及最终的治疗和伦理意义具有重要作用。此外，针对痴呆主要临床形式（阿尔茨海默病 - AD和额颞叶痴呆 - FTD）的遗传学研究方法为帮助家庭应对这些复杂性提供了临床指南。AD和FTD是多因素、遗传复杂的疾病，涉及许多候选基因。三个基因（即淀粉样前体蛋白，APP；早老素1，PSEN1；早老素2，PSEN2）的突变与所有家族性AD（FAD）形式的50%相关。全基因组关联研究（GWAS）涉及越来越多可能在疾病发病机制中起作用的基因。到目前为止，家族性FTD的遗传学与7个基因有关：微管相关蛋白tau（MAPT）、原颗粒蛋白（GRN）、含缬酪肽蛋白（VCP）、染色质修饰2B（CHMP2B）、TARDNA结合蛋白43编码基因（TARBDP）、肉瘤融合蛋白（FUS）以及9号染色体开放阅读框中的最后六核苷酸重复序列（C9orf72）。在患者及其无症状的高危家庭成员中，检测前咨询和基因缺陷的识别都很重要。
