Premium
Autosomal dominant early onset Alzheimer's disease in the Mexican state of Jalisco: High frequency of the mutation PSEN1 c. 1292C >A and phenotypic profile of patients
Author(s) -
DumoisPetersen Sofia,
GallegosArreola Martha P.,
MagañaTorres María T.,
PereaDíaz Francisco J.,
Ringman John M.,
Figuera Luis E.
Publication year - 2020
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31865
Subject(s) - psen1 , mutation , early onset alzheimer's disease , founder effect , disease , population , age of onset , medicine , genetics , alzheimer's disease , presenilin , biology , gene , genotype , environmental health , haplotype
Mutations in three genes ( APP, PSEN1, and PSEN2 ) are the main cause of the autosomal dominant early‐onset Alzheimer's disease (AD‐EOAD). In PSEN1, the A431E (c.1292C>A, rs63750083) mutation is suspected to have exerted a founder effect in the State of Jalisco, Mexico. In Guadalajara, Jalisco, Mexico, this mutation was found in 46 index cases evaluated for AD‐EOAD. In our genealogical analysis, 301 affected relatives of the mutation carriers were identified, 195 of whom were already deceased at the time of interview. Moreover, 560 descendants had a 50% risk of carrying the mutation, and 348 were potentially at risk. A systematic phenotyping was performed in 39 patients. The mean onset age was 42.5 ± 3.9 years, and no significant difference in onset age was observed between the male and female patients. Furthermore, a substantial clinical heterogeneity and high frequencies of spastic paraparesis, language disorders, and neuropsychiatric symptoms were observed. To our knowledge, the investigated families represent the second biggest population carrying a PSEN1 mutation in Latin America, offering a unique opportunity to study the genetic basis of Alzheimer's disease. Addressing AD‐EOAD warrants an integral approach involving a deep understanding of its clinical behavior, as well as counseling protocols and prevention studies.