NOVEL, PSEN1 T119I MUTATION IN AN EARLY-ONSET ALZHEIMER'S DISEASE PATIENT

Abstract

Alzheimer’s disease is the most common form of senile dementia, occurs mostly in the elder ages. Early onset form of disease could be associated with genetics, where 3 genes were established to play role in disease onset: APP, PSEN1, and PSEN2. PSEN1 is the most common causative gene for EOAD. Next generation sequencing approaches have been performed with a gene panel of 50 neurodegenerative disease-associated genes, published last year. 100 EOAD patients were screened, and the mutations were verified by standard sequencing and SSCP studies. A novel mutation T119I was found in one of the EOAD patient. This mutation was not reported any of the known EOAD mutation databases, neither in the HapMap or ExAC database. In silico modeling will be performed on its pathogenic nature. More studies are needed on PSEN1 T119I, however, since it is located on the conservative TM-I, it might be possible that this variant could result significant changes in PSEN1. A similar mutation PSEN1 T116I was already reported, which was established as pathogenic mutation. This could be evidence that PSEN1 T119I could be a pathogenic mutation.