Variability of the clinical phenotype in an italian family with dementia associated with an intronic deletion in the GRN gene

Gabriella Marcon, Giacomina Rossi, Giorgio Giaccone, Anna Rita Giovagnoli, Elena Piccoli, Sergio Zanini, Onelio Geatti, Vito Toso, Marina Grisoli, Fabrizio Tagliavini

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5-8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cerebral atrophy. Our data extend the phenotypic spectrum and the complexity of neurodegenerative diseases linked to GRN mutations.

Original languageEnglish
Pages (from-to)583-590
Number of pages8
JournalJournal of Alzheimer's Disease
Volume26
Issue number3
DOIs
Publication statusPublished - 2011

Keywords

  • Alzheimer's disease
  • frontotemporal dementia
  • haploinsufficiency
  • mutation
  • phenotype
  • progranulin

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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