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
| Autor: | Francisco Javier Perea-Díaz, María Teresa Magaña-Torres, Luis E. Figuera, Sofia Dumois-Petersen, Martha Patricia Gallegos-Arreola, John M. Ringman |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
education.field_of_study Pediatrics medicine.medical_specialty business.industry Population Disease 030105 genetics & heredity medicine.disease Phenotype 03 medical and health sciences 030104 developmental biology Mutation (genetic algorithm) PSEN2 Genetics medicine PSEN1 Early-onset Alzheimer's disease education business Genetics (clinical) Founder effect |
| Zdroj: | American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 184:1023-1029 |
| ISSN: | 1552-4876 1552-4868 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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