AUTHOR=Jiang Bin , Bi Min , Li Jun , Liu Qi , Xiao Nai-An , Fang Jie , Shi Man-Yi , Yu Zi-Wen , Ma Qi-Lin , Tong Sui-Jun , Zheng Kun-Mu 

TITLE=A Pathogenic Variant p.Phe177Val in PSEN1 Causes Early-Onset Alzheimer’s Disease in a Chinese Family

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00713

DOI=10.3389/fgene.2020.00713

ISSN=1664-8021

ABSTRACT=<p>Familial Alzheimer’s disease (FAD) present as a positive family history of cognitive decline, with early onset and an autosomal dominant inheritance pattern. FAD is mainly caused by the mutations in the genes encoding for amyloid precursor protein (<italic>APP</italic>), presenilin-1 (<italic>PSEN1</italic>), and presenilin-2 (<italic>PSEN2</italic>). In the present study, we identified a variant (c.529T &gt; G, p.Phe177Val) in <italic>PSEN1</italic> across three generations in a Chinese family with FAD using whole-exome sequencing. The mean age of onset was 39 years (range: 37 to 40 years) in this family. In cell transfection studies, the mutant PSEN1 protein carrying p.Phe177Val increased both the production of Aβ42 and the ratio of Aβ42 over Aβ40, as compared to wild-type PSEN1. Our results confirm the pathogenicity of <italic>PSEN1</italic> p.Phe177Val variant in FAD and broaden the clinical phenotype spectrum of FAD patients with <italic>PSEN1</italic> p.Phe177Val variant.</p>