Medical School, University of Cyprus, Nicosia, Cyprus and Department of Neurology, General Hospital of Nicosia, Nicosia 2029, Cyprus.
Department of Neurology, University Hospital of Larissa, 41334 Larissa, Greece.
Int J Mol Sci. 2021 Nov 16;22(22):12355. doi: 10.3390/ijms222212355.
Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer's disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T>G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 ± 8.3 (31-80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the β-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous.
编码淀粉样前体蛋白（APP）的基因突变导致常染色体显性遗传性阿尔茨海默病（AD）。我们报告了一例 68 岁女性患者，她表现为癫痫发作、神经精神症状和进行性记忆减退，并携带一种新的 APP 变体 c.2062T>G pLeu688Val。在 PubMed 和 Web of Science 数据库中对所有报道的 APP 突变引起的 AD 病例进行了全面的文献回顾。我们共回顾了 98 项研究，共计 385 例。疾病发病的平均年龄为 51.3±8.3（31-80 岁）。突变最常位于外显子 17（80.8%）和 16（12.2%）。最常见的症状是痴呆、视觉空间症状、失语症、癫痫和精神症状。β-淀粉样蛋白区域的突变，特别是外显子 17 的突变，与高致病性和更年轻的发病年龄相关。我们描述了在希腊人群中发现的第二个 APP 突变。APP 突变可能对疾病的表现有不同的影响，其表型具有异质性。
