期刊
MOLECULAR GENETICS & GENOMIC MEDICINE
卷 2, 期 5, 页码 430-437出版社
WILEY
DOI: 10.1002/mgg3.85
关键词
Alzheimer's disease; Caribbean Hispanics; familial dementia; mutations; next-generation sequencing
资金
- National Institute of Health and the National Institute on Aging [R37-AG15473, P01AG07232]
- Blanchette Hooker Rockefeller Foundation
- Banbury Fund
- Merrill Lynch Foundation
- Paul B. Beeson Career Development Award [K23AG034550]
Pathogenic mutations in the three known genes -the amyloid precursor protein (APP), presenilin 1 (PSEN1), presenilin 2 (PSEN2) - are known to cause familial Alzheimer's disease (AD) and tend to be associated with early-onset AD. However, the frequency and risk associated with these mutations vary widely. In addition, mutations in the frontotemporal lobar degeneration (FTLD) genes -the microtubule-associated protein tau (MAPT), granulin (GRN) -have also been found to be associated with clinical AD. Here, we conducted targeted resequencing of the exons in genes encoding APP, PSEN1, PSEN2, GRN, and MAPT in 183 individuals from families with four or more affected relatives, presumed to be AD, and living in the Dominican Republic and Puerto Rico. We then performed linkage and family-based association analyses in carrier families, and genotyped 498 similarly aged unrelated controls from the same ethnic background. Twelve potentially pathogenic mutations were found to be associated with disease in 53 individuals in the five genes. The most frequently observed mutation was the p. Gly206Ala variant in PSEN1 present in 30 (57%) of those sequenced. In the combined linkage and association analyses several rare variants were associated with dementia. In Caribbean Hispanics with familial AD, potentially pathogenic variants were present in 29.2%, four were novel mutations, while eight had been previously observed. In addition, some family members carried variants in the GRN and MAPT genes which are associated with FTLD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据