Affiliations: [a] Center for Neurodegenerative Diseases (CEMAND); Department of Medicine, Surgery and Dentistry, Neuroscience Section, University of Salerno, Italy
| [b]
Institute of Biochemistry and Cell Biology (IBBC), CNR, Naples, Italy
| [c] Department of Biology, University of Naples Federico II, Naples, Italy
| [d] Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia | [e] Department of Molecular Medicine, University of Pavia, Pavia, Italy
| [f] IRCCS Mondino Foundation, Pavia, Italy
Correspondence:
[*]
Correspondence to: Emilia Vitale, PhD, Institute of Biochemistry and Cell Biology (IBBC), CNR, Naples, Italy. Tel.: +39 081 6132 218; Fax: +39 081 6132 277; E-mail: emilia.vitale@cnr.it.
Note: [1] Responsible for the DEMENTIA-BIOBANK.
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.
