One novel GRN null mutation, two different aphasia phenotypes(43 visite) Coppola C, Oliva M, Saracino D, Pappata S, Zampella E, Cimini S, Ricci M, Giaccone G, Di Iorio G, Rossi G
Neurobiol Aging (ISSN: 0197-4580linking, 1558-1497electronic), 2019 Nov 12; N/D: N/D-N/D.
Tipo di articolo: Journal Article,
Impact factor: 2.872, Impact factor a 5 anni: 5.999
Url: Non disponibile.
Parole chiave: Frontotemporal Lobar Degeneration
, Primary Progressive Aphasia
, Progranulin Protein
, Progressive Nonfluent Aphasia,
*** IBB - CNR *** Second Division of Neurology, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: firstname.lastname@example.org. Department of Biomedical Sciences, Institute of Biostructure and Bioimaging, National Council of Research, Naples, Italy. Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy.
Progranulin gene (GRN) mutations are among the leading causes of frontotemporal lobar degeneration, a group of neurodegenerative diseases characterized by remarkable clinical heterogeneity. In this article, we report the new GRN 708+4A>T splicing mutation, identified in 2 siblings of a family with several members affected by cognitive, behavioral, and motor disorders. Plasma progranulin dosage and GRN expression analysis, together with in silico prediction studies, supported the pathogenicity of the mutation. Both the patients displayed a clinical syndrome in which language impairment was largely predominant. However, motor speech deficits were the major feature in one case, diagnosed as progressive nonfluent aphasia, whereas marked semantic alterations were present in the other, whose clinical phenotype was in favor of a mixed aphasia. The profile of neuroanatomical alterations from imaging studies was in line with the clinical phenotypes. Therefore, also this novel GRN mutation is associated with haploinsufficiency and phenotypic heterogeneity, which are both typical features of progranulinopathies.<br>