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.
Clinical and Molecular Characterization of a Novel Progranulin Deletion Associated with Different Phenotypes / Picillo, M.; Vitale, E.; Rendina, A.; Donizetti, A.; Aliperti, V.; Tepedino, M. F.; Dati, G.; Ginevrino, M.; Valente, E. M.; Barone, P.. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1875-8908. - 76:1(2020), pp. 341-347. [10.3233/JAD-200151]
Clinical and Molecular Characterization of a Novel Progranulin Deletion Associated with Different Phenotypes
Picillo M.;Donizetti A.;Aliperti V.;
2020
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
