P4-105: PROGRANULIN C.709-1G>A VARIANT IN AN ARGENTINE FAMILY WITH BEHAVIORAL VARIANT FRONTOTEMPORAL DEMENTIA AND SEMANTIC PRIMARY PROGRESSIVE APHASIA

Mutations in GRN are a frequent genetic cause of frontotemporal lobar degeneration. In this study we describe the finding of GRN variant c.709-1G>A (p.Ala237fs) in an Argentine family of Basque origin with a history of behavioral variant frontotemporal dementia (bvFTD) and semantic primary progressive aphasia (svPPA). Whole exome and Sanger sequencing validation were performed on the proband's genomic DNA obtained from a blood sample. The patient underwent clinical and neuropsychological evaluations as well as brain imaging. The latter included: nuclear magnetic resonance (NMR) and positron emission tomography (PET) using radiotracers: F-18-2-fluoro-2-deoxy-D-glucose (FDG) and Pittsburgh Compound B (PiB). The proband was diagnosed at age 56 with svPPA. Family history included a sibling with bvFTD (age of onset: 48 years) who died seven years after diagnosis. Exome sequencing revealed a heterozygous G>A mutation in the splice acceptor site of GRN intron 7 (c.709-1G>A). This mutation had been previously reported in FTD patients from the Basque region (López de Munain A, 2008). NMR analysis revealed bilateral frontal cortex atrophy, while FDG-PET showed frontal cortex hypometabolism. We report the first family in Latin America with the pathogenic c.709-1G>A variant in GRN.