Novel P397S MAPT variant associated with late onset and slow progressive frontotemporal dementia

• Published in: Annals of clinical and translational neurology 2019-08, Vol.6 (8), p.1559-1565
• Main Authors: Borrego‐Écija, Sergi, Antonell, Anna, Puig‐Butillé, Joan Anton, Pericot, Inmaculada, Prat‐Bravo, Carme, Abellan‐Vidal, Maria Teresa, Mallada, Javier, Olives, Jaume, Falgàs, Neus, Oliva, Rafael, Lladó, Albert, Sánchez‐Valle, Raquel
• Format: Article
• Language: English
• Subjects: Age; Age of Onset; Aged; Alzheimer's disease; Atrophy; Behavior; Biomarkers; Brain - physiology; Brief Communication; Brief Communications; Dementia; Family medical history; Female; Frontotemporal Dementia - genetics; Frontotemporal Dementia - physiopathology; Genetic counseling; Genotype; Genotype & phenotype; Humans; Laboratories; Male; Memory; Middle Aged; Mutation; Neuropathology; Pathology; Semantics; Siblings; tau Proteins - genetics; Wills
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.50844

Mutations in the MAPT gene cause frontotemporal dementia with tau deposits. We report the novel p.P397S MAPT variant in eight subjects from five apparently nonrelated families suffering from frontotemporal dementia with autosomal dominant pattern of inheritance. In silico analysis reported conflicting evidence of pathogenicity. The segregation analysis support that this variant is likely pathogenic. The mean age at onset (61.4 years) and mean disease duration (13.9 years) of these subjects and their affected relatives were significantly higher compared with our series of p.P301L MAPT mutation carriers. These findings suggest that p.P397S variant could be a new MAPT mutation associated with a less aggressive phenotype than other MAPT mutations.