A novel mutation in PSEN1 (p.T119I) in an Argentine family with early- and late-onset Alzheimer's disease

Abstract

Mutations inPSEN1are the most common cause of early-onset Alzheimer’s disease (AD). In this article,we present an Argentine family with autosomal dominant early- and late-onset AD. The proband and 6family members were available for genetic testing and clinical and neuropsychological assessments.Cerebrospinalfluid biomarkers were analyzed in the proband and a cousin (mutation carrier), who alsounderwent positron emission tomography using F-18-2-fluoro-2-deoxy-D-glucose and Pittsburghcompound B. Exon sequencing ofPSEN1,PSEN2, andAPPrevealed a novel heterozygous variant inPSEN1(c.356C>T; p.T119I). Median age of onset in the family was 56 years. However, the proband’s uncleshowed initial symptoms at age 71. Although no DNA was available, he was an obligate carrier becausehis daughter (proband’s cousin) carried the mutation. Both the proband and his cousin exhibitedbiomarker evidence (cerebrospinalfluid or imaging) of underlying Alzheimer’s pathology. Overall, ourresults support that thePSEN1p.T119I variant is likely pathogenic.