Department of Experimental Medicine, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy,
Molecular Genetics Unit, IRCCS Neuromed, Pozzilli, Italy.
Neurodegener Dis. 2019;19(2):96-100. doi: 10.1159/000502906. Epub 2019 Oct 2.
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.
载脂蛋白 APP 基因突变导致的阿尔茨海默病（AD）呈常染色体显性遗传模式。我们报告了一例 40 岁女性，自 36 岁起出现严重认知能力下降，而其受影响的亲属则在 60 岁以后出现症状。先证者携带 APP 错义变异纯合子（NM_000484.4：c.2032G>A；NP_000475.1：p.Asp678Asn；rs63750064），与其他 AD 亲属相比，其发病年龄和疾病进展速度更为严重。该突变表现为半显性特征。在纯合状态下研究载脂蛋白 APP 突变的罕见机会表明，它们并不总是显性的，可能存在其他分离模式。
