Whole-Exome Sequencing and C9orf72 Analysis in Primary Progressive Aphasia

J Alzheimers Dis. 2021;80(3):985-990. doi: 10.3233/JAD-201310.

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; MAPT protein; frontotemporal degeneration; genetics; primary progressive aphasia; progranulin.

Publication types

  • Letter

MeSH terms

  • Aged
  • Aphasia, Primary Progressive / genetics*
  • C9orf72 Protein / genetics*
  • Exome Sequencing
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Progranulins / genetics
  • Sequestosome-1 Protein / genetics

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • GRN protein, human
  • Progranulins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein