APP gene mutations causing Alzheimer disease (AD) segregate in an autosomal dominant pattern. We report on a 40-year-old woman with a severe cognitive decline starting at 36 years, while her affected relatives presented symptoms onset in the 6th decade. The proband carried an APP missense variant in homozygous state (NM_000484.4: c.2032G>A; NP_000475.1: p.Asp678Asn; rs63750064) and showed a more severe clinical picture than the other AD relatives, as regards the age of onset and the rate of disease progression. This mutation behaves as a semi-dominant trait. The very rare chance of studying APP mutations in the homozygous state demonstrates they are not always dominant and other segregation models are possible.
Unusual Segregation of APP Mutations in Monogenic Alzheimer Disease / Mastromoro, Gioia; Gambardella, Stefano; Marchionni, Enrica; Campopiano, Rosa; Traversa, Alice; DI BONAVENTURA, Carlo; Pizzuti, Antonio. - In: NEURODEGENERATIVE DISEASES. - ISSN 1660-2854. - 2:(2019). [10.1159/000502906]