Larner A J, Doran M
Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery Fazakerley, Liverpool, UK.
J Neurol. 2006 Feb;253(2):139-58. doi: 10.1007/s00415-005-0019-5. Epub 2005 Nov 4.
It is now 10 years since the first report of mutations in the presenilin genes that were deterministic for familial autosomal dominant Alzheimer's disease. The most common of these mutations occurs in the presenilin-1 gene (PSEN1) located on chromosome 14. In the ensuing decade, more than 100 PSEN1 mutations have been described. The emphasis of these reports has largely been on the novelty of the mutations and their potential pathogenic consequences rather than detailed clinical, neuropsychological, neuroimaging and neuropathological accounts of patients with the mutation. This article reviews the clinical phenotypes of reported PSEN1 mutations, emphasizing their heterogeneity, and suggesting that other factors, both genetic and epigenetic,must contribute to disease phenotype.
自首次报道早老素基因的突变可导致家族性常染色体显性阿尔茨海默病以来，已经过去了10年。这些突变中最常见的发生在位于14号染色体上的早老素-1基因（PSEN1）中。在随后的十年里，已经描述了100多种PSEN1突变。这些报告主要强调了突变的新颖性及其潜在的致病后果，而不是对携带该突变患者的详细临床、神经心理学、神经影像学和神经病理学描述。本文回顾了已报道的PSEN1突变的临床表型，强调了它们的异质性，并表明其他遗传和表观遗传因素必定对疾病表型有影响。
