ISSN: 2657-7941
Archives of Medical Science - Aging
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1/2021
vol. 4
 
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abstract:
Clinical research

Identification of novel missense mutations (c.1156T>C and c.785T>C) in the PSEN1 gene in Chinese families with early-onset Alzheimer’s disease

Lu Ren
1, 2
,
Qiuyan Wang
3
,
Guowen Min
3
,
Yarong Zhao
3
,
Yang Li
3

1.
First Clinical Medical College, Shanxi Medical University, Taiyuan, China
2.
Department of Neurology; Lvliang People’s Hospital; Lvliang City, China
3.
Department of Neurology, First Clinical Medical College, Shanxi Medical University, Taiyuan, China
Arch Med Sci Aging 2021; 4: e6–e13
Online publish date: 2021/06/30
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Introduction
Mutations in the presenilin 1 (PSEN1) gene are associated with the inherited form of early-onset Alzheimer’s disease (AD). Currently, more than 200 PSEN1 mutations have been identified.

Material and methods
Two Chinese families with early-onset Alzheimer’s disease were enrolled in this study. Their clinical and radiological profiles were analyzed, and their genomic DNA was extracted from peripheral blood and amplified for sequencing. The sequences of all exons and intron/exon boundaries in the PSEN1 gene were analyzed. The potential pathogenicity of the identified mutations was predicted using the SIFT and PolyPhen-2 bioinformatics software tools.

Results
In the first family, a novel heterozygous missense mutation (c.1156T>A) was identified in exon 11 of the PSEN1 gene. This nucleotide substitution led to an amino acid change from phenylalanine to leucine at codon 386 (p.F386L), and was predicted to be ‘deleterious’ by SIFT and ‘probably damaging’ by PolyPhen-2. This mutation was not consistent across all family members with the disease. In the second family, a novel heterozygous missense mutation (c.785T>C) was identified in exon 8 of the PSEN1 gene, which also caused an amino acid change (p.L262S). This mutation was also predicted to be ‘deleterious’ by SIFT and ‘probably damaging’ by PolyPhen-2.

Conclusions
We identified two novel heterozygous missense mutations (c.1156T>C and c.785T>C) in the PSEN1 gene in separate Chinese families with early-onset Alzheimer’s disease. This study provides new PSEN1 gene mutation profiles, which help to elucidate the pathogenesis of early-onset Alzheimer’s disease.

keywords:

early-onset Alzheimer’s disease, presenilin 1, PSEN1, mutation, DNA sequencing, Chinese

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