Clinical and Molecular Characterization of a Novel Progranulin Deletion Associated with Different Phenotypes

J Alzheimers Dis. 2020;76(1):341-347. doi: 10.3233/JAD-200151.

Abstract

Background: Mutations in the GRN gene are causative for an autosomal dominant form of frontotemporal dementia.

Objective/methods: The objective of the present study is to describe clinical and molecular features of three siblings harboring the GRN deletion NM_002087.3:c.295_308delTGCCCACGGGGCTT, p.(Cys99Profs*15) identified with next generation sequencing.

Results: Our patients demonstrated heterogeneous clinical phenotypes, such as progressive supranuclear palsy-like in the proband and the behavioral variant of frontotemporal dementia in the two affected siblings. Progranulin haploinsufficiency was revealed by both gene expression and protein analyses.

Conclusion: The pathogenicity of the novel GRN deletion c.295_308del TGCCCACGGGGCTT is confirmed by both functional analysis and segregation in three affected siblings.

Keywords: Dementia; gene; genetics; parkinsonism; progranulin; progressive supranuclear palsy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Frontotemporal Dementia / diagnostic imaging*
  • Frontotemporal Dementia / genetics*
  • Gene Deletion*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Progranulins / genetics*

Substances

  • GRN protein, human
  • Progranulins