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

NIIKADO, MATÍAS; CALANDRI, ISMAEL; BARBIERI-KENNEDY, MICAELA; ITZCOVICH, TATIANA; MARTINETTO, HORACIO; VAZQUEZ, SILVIA; ALLEGRI, RICARDO; SEVLEVER, GUSTAVO; SURACE, EZEQUIEL I.

Los Angeles

Conferencia; Alzheimer's Association International Conference; 2019

Alzheimer's Association

Background: Mutations in GRN are a frequent genetic cause offrontotemporal lobar degeneration. In this study we describe thefinding of GRN variant c.709-1G>A (p.Ala237fs) in an Argentinefamily of Basque origin with a history of behavioral variant frontotemporaldementia (bvFTD) and semantic primary progressiveaphasia (svPPA). Methods: Whole exome and Sanger sequencingvalidation were performed on the proband?s genomic DNA obtainedfrom a blood sample. The patient underwent clinical andneuropsychological evaluations as well as brain imaging. The latterincluded: nuclear magnetic resonance (NMR) and positron emissiontomography (PET) using radiotracers: F-18-2-fluoro-2-deoxy-D-glucose (FDG) and Pittsburgh Compound B (PiB). Results:The proband was diagnosed at age 56 with svPPA. Familyhistory included a sibling with bvFTD (age of onset: 48 years)who died seven years after diagnosis. Exome sequencing revealeda heterozygous G>A mutation in the splice acceptor site of GRNintron 7 (c.709-1G>A). This mutation had been previously reportedin FTD patients from the Basque region (Lopez de MunainA, 2008). NMR analysis revealed bilateral frontal cortex atrophy,while FDG-PET showed frontal cortex hypometabolism. Conclusions:We report the first family in Latin America with the pathogenicc.709-1G>A variant in GRN.