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.