Genetic screening in two Iranian families with early-onset Alzheimer’s disease identified a novel PSEN1 mutation

Introduction: Among these, Alzheimer’s disease (AD) is the most common cause of dementia and a subset ofEOAD is inherited as an autosomal-dominant trait. In this study, we clinically examined 2 Iranian families withADAD and performed a genetic screen for pathogenic mutations in APP, PSEN1, and PSEN2 genes. Two PSEN1mutations were identified as likely disease-causing mutations.Materials and methods: We screened exons containing known pathogenic AD mutations by using primer pairsflanking coding exons of APP, PSEN1, and PSEN2. The pathogenicity of the novel PSEN1 missense mutation waspredicted by several computational methods, including MutPred,SNPs&GO, MutationTaster and SIFT.Results: Our sequencing analysis revealed that the affected individual from Family 1 carried a novel PSEN1mutation (c.424G> T, exon 5). This mutation was found to be absent in the 2 available unaffected individuals and in87 ethnicity-matched neurologically normal individuals.. The PSEN1 Val142Phe mutation was not reported in thegnomAD or the Alzheimer Disease & Frontotemporal Dementia MutationDatabase. This novel variant is predicted tobe pathogenic by several different computational methods.Conclusion: we report the first PSEN1 mutations described in the Iranian population.These findings are consistentwith what has been previously described in patients with PSEN1 mutations and expand the mutational spectrum ofPSEN1-associated disease.

کلیدواژه ها:

PSEN1 mutation ، Early-onset Alzheimer’s disease ، Rapid disease progression