Open AccessTwo Novel Mutations and a de novo Mutation in PSEN1 in Early-onset Alzheimer’s Disease
Author(s) -
Yusheng Li,
Zhihua Yang,
Yao Zhang,
Jing Yang,
Donghao Shang,
Shuyu Zhang,
Jun Wu,
Jing Yan,
Lu Zhao,
Changhe Shi,
Yuming Xu
Publication year - 2019
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2018.1109
Subject(s) - psen1 , presenilin , early onset alzheimer's disease , genetics , mutation , sanger sequencing , alzheimer's disease , phenotype , disease , biology , exon , medicine , bioinformatics , gene , pathology
Presenilin 1 ( PSEN1 ), presenilin 2 ( PSEN2 ), and amyloid precursor protein ( APP ) mutations are responsible for autosomal dominant early-onset Alzheimer's disease (AD-EOAD). To analyze the phenotypes and genotypes of EOAD patients, we performed comprehensive clinical assessments as well as mutation screening of PSEN1 , PSEN2 , and exons 16 and 17 of APP by Sanger sequencing in the three Chinese EOAD families. We identified two novel mutations of PSEN1 (Y256N and H214R) in samples from these families, and a de novo mutation of PSEN1 (G206V) in a patient with very early-onset sporadic Alzheimer's disease. A combination of bioinformatics tools based on evolutionary, structural and computational methods predicted that the mutations were all deleterious. These findings suggest that PSEN1 Y256N, H214R, and G206V need to be considered as potential causative mutations in EOAD patients. Further functional studies are needed to evaluate the roles of these mutations in the pathogenesis of AD.