Background: The objective of this study was to describe the clinical features and the genetic analysis of a family with autosomal-dominant familial Alzheimer's disease.
Patients and method: In addition to the clinical findings of different family members, we performed a genetic analysis to detect mutations in the amyloid precursor protein genes, presenilin 1 and presenilin 2 genes, by means of single-strand conformation polymorphism and subsequent sequencing. The APOE genotype was also determined.
Results: The proband was a 52-year-old patient whose Alzheimer's disease started at age 49 years. Family history revealed that several members had developed an early onset dementia. The clinical picture in all them was characterized by cognitive and behavioral abnormalities that started at age 40 to 50 years. An important variability in the age of onset was observed among family members (range 39-51 years). The proband's genetic study identified a mutation in the presenilin 1 gene which predicted a methionine-to-treonine substitution at codon 139 (M139T). APOE genotype was *3/*3.
Conclusions: The clinical picture of this family carrying the M139T mutation was similar to that of the sporadic variant of Alzheimer's disease. The observed variability in the age of onset suggests that, yet being genetically determined, other genetic or environmental factors modify the clinical expression of the disease.