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A Rare Intronic Variation of Presenilin-1 (rs201992645) is Associated with Alzheimer’s Disease and Down Syndrome Birth

Pranami Bhaumik, Priyanka Ghosh, Sujoy Ghosh, Kausik Majumdar, Sandip Pal, Biswanath Sarkar, AbhishiktaGhosh Roy, Abhinandan Chakraborty and Subrata Kumar Dey

Background and objective: Presenilin-1 (PSEN-1) gene is a potent candidate that relates Alzheimer’s disease (AD) to Down syndrome (DS). Genetic variation of PSEN-1 could be a risk factor that predisposes individual for both AD and DS and may contribute the common etiology of both the disorders. Methods: We sequenced exon 8 of PSEN-1 with flanking introns in 136 DS patients with their parents, 96 AD patients, 173 age-matched controls. Results were analysed in-silico to anticipate the damaging effect at molecular level. Results: A rare polymorphism rs201992645 was identified within intron 8 and in silico analysis revealed the variation as ‘potentially damaging’ at the transcript splicing level. The genotypic frequencies of mutant heterozygotes were 0.031, 0.029 and 0.029 for AD, DS and mother of DS respectively. Conclusions: We have suggested that this variation may cause AD manifestation in mothers of DS patients and is the potential marker for predisposition testing of both disorders.