Clinical and Molecular Characterization of a Novel Progranulin Deletion Associated with Different Phenotypes.
Dementia
gene
genetics
parkinsonism
progranulin
progressive
supranuclear palsy
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
1
6
2020
medline:
8
5
2021
entrez:
1
6
2020
Statut:
ppublish
Résumé
Mutations in the GRN gene are causative for an autosomal dominant form of frontotemporal dementia. 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. 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. The pathogenicity of the novel GRN deletion c.295_308del TGCCCACGGGGCTT is confirmed by both functional analysis and segregation in three affected siblings.
Sections du résumé
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.
Identifiants
pubmed: 32474471
pii: JAD200151
doi: 10.3233/JAD-200151
doi:
Substances chimiques
GRN protein, human
0
Progranulins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM