Whole-Exome Sequencing and C9orf72 Analysis in Primary Progressive Aphasia

Article type: Short Communication

Authors: Pytel, Vanesa^{a; b} | Hernández-Lorenzo, Laura^{a; b} | Torre-Fuentes, Laura^b | Sanz, Raúl^c | González, Nieves^c | Cabrera-Martín, María Nieves^d | Delgado-Álvarez, Alfonso^a | Gómez-Pinedo, Ulises^b | Matías-Guiu, Jorge^{a; b} | Matias-Guiu, Jordi A^{a; *}

Affiliations: [a] Department of Neurology, Hospital Clinico San Carlos, Health Research Institute “San Carlos” (IdISCC), Universidad Complutense de Madrid, Madrid, Spain | [b] Laboratory of Neurobiology, Hospital Clinico San Carlos. Health Research Institute “San Carlos” (IdISCC), Universidad Complutense de Madrid, Madrid, Spain | [c] Center of Genetic Studies ATG Medical, Madrid, Spain | [d] Department of Nuclear Medicine, Hospital Clinico San Carlos, Health Research Institute “San Carlos” (IdISCC), Universidad Complutense de Madrid, Madrid, Spain

Correspondence: [*] Correspondence to: Dr. Jordi A Matias-Guiu, Department of Neurology, Hospital Clinico San Carlos, Prof. Martin Lagos St, 28040, Madrid, Spain. Tel.: +34676933312.; E-mails: jordimatiasguiu@hotmail.com, jordi.matias-guiu@salud.madrid.org

Abstract: Primary progressive aphasia (PPA) is mainly considered a sporadic disease and few studies have systematically analyzed its genetic basis. We here report the analyses of C9orf72 genotyping and whole-exome sequencing data in a consecutive and well-characterized cohort of 50 patients with PPA. We identified three pathogenic GRN variants, one of them unreported, and two cases with C9orf72 expansions. In addition, one likely pathogenic variant was found in the SQSTM1 gene. Overall, we found 12%of patients carrying pathogenic or likely pathogenic variants. These results support the genetic role in the pathophysiology of a proportion of patients with PPA.

Keywords: Alzheimer’s disease, C9orf72 protein, frontotemporal degeneration, genetics, MAPT protein, primary progressive aphasia, progranulin

DOI: 10.3233/JAD-201310

Journal: Journal of Alzheimer's Disease, vol. 80, no. 3, pp. 985-990, 2021