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 journalArticle

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

Fingerprint

Dementia
Phenotype
Mutation
Frontotemporal Dementia
Genes
Haploinsufficiency
Neurologic Examination
Neurodegenerative Diseases
Atrophy
Alzheimer Disease
Messenger RNA

Keywords

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

ASJC Scopus subject areas

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

Cite this

Variability of the clinical phenotype in an italian family with dementia associated with an intronic deletion in the GRN gene. / Marcon, Gabriella; Rossi, Giacomina; Giaccone, Giorgio; Giovagnoli, Anna Rita; Piccoli, Elena; Zanini, Sergio; Geatti, Onelio; Toso, Vito; Grisoli, Marina; Tagliavini, Fabrizio.

In: Journal of Alzheimer's Disease, Vol. 26, No. 3, 2011, p. 583-590.

Research output: Contribution to journalArticle

@article{5b9dfabe93fc4ac6afa4be746f8b9571,
title = "Variability of the clinical phenotype in an italian family with dementia associated with an intronic deletion in the GRN gene",
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.",
keywords = "Alzheimer's disease, frontotemporal dementia, haploinsufficiency, mutation, phenotype, progranulin",
author = "Gabriella Marcon and Giacomina Rossi and Giorgio Giaccone and Giovagnoli, {Anna Rita} and Elena Piccoli and Sergio Zanini and Onelio Geatti and Vito Toso and Marina Grisoli and Fabrizio Tagliavini",
year = "2011",
doi = "10.3233/JAD-2011-110332",
language = "English",
volume = "26",
pages = "583--590",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "3",

}

TY - JOUR

T1 - Variability of the clinical phenotype in an italian family with dementia associated with an intronic deletion in the GRN gene

AU - Marcon, Gabriella

AU - Rossi, Giacomina

AU - Giaccone, Giorgio

AU - Giovagnoli, Anna Rita

AU - Piccoli, Elena

AU - Zanini, Sergio

AU - Geatti, Onelio

AU - Toso, Vito

AU - Grisoli, Marina

AU - Tagliavini, Fabrizio

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - frontotemporal dementia

KW - haploinsufficiency

KW - mutation

KW - phenotype

KW - progranulin

UR - http://www.scopus.com/inward/record.url?scp=80053488727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053488727&partnerID=8YFLogxK

U2 - 10.3233/JAD-2011-110332

DO - 10.3233/JAD-2011-110332

M3 - Article

C2 - 21677378

AN - SCOPUS:80053488727

VL - 26

SP - 583

EP - 590

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 3

ER -