Systematic genetic study of Alzheimer disease in Latin America : mutation frequencies of the amyloid <tex>$\beta$</tex> precursor protein and presenilin genes in Colombia
Van Broeckhoven, Christine
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
New York, N.Y.
American journal of medical genetics. - New York, N.Y., 1977 - 2002
American journal of medical genetics: part B: neuropsychiatric genetics. - Bognor Regis
, p. 138-143
University of Antwerp
Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset less than or equal to 65 years). No APP missense mutations were identified. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in five AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations. (C) 2001 Wiley-Liss, Inc.