Mutations in progranulin gene (GRN) are a common cause of autosomal dominant frontotemporal lobar degeneration syndromes and are associated with a wide phenotypic heterogeneity. The majority of genetic defects in GRN consists of loss-of-function mutations, causing haploinsufficiency, and is associated with extremely low plasma progranulin levels. Herein, we describe a patient who developed language dysfunctions and memory disturbances at 63 years of age. Considering the early onset and the positive family history (sister aged 50 with non-fluent/agrammatic variant of primary progressive aphasia, father with behavioral disturbances in his sixties), a genetic analysis was carried out, showing the presence of a novel mutation [g.9543delA (IVS3-2delA)] in a predicted splicing site of GRN. Her progranulin plasma levels were under the reference threshold, as in her sister, thus supporting the causative role of the new variant. The same genetic mutation was confirmed by sequencing in her sister. Results described enlarge current knowledge on genetic causes of the disease and clinical characteristics of carriers.

Non Fluent Variant of Primary Progressive Aphasia Due to the Novel GRN g.9543delA(IVS3-2delA) Mutation / S.M.G. Cioffi, D. Galimberti, F. Barocco, M. Spallazzi, C. Fenoglio, M. Serpente, M. Arcaro, S. Gardini, E. Scarpini, P. Caffarra. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 54:2(2016 Sep 06), pp. 717-721. [10.3233/JAD-160185]

Non Fluent Variant of Primary Progressive Aphasia Due to the Novel GRN g.9543delA(IVS3-2delA) Mutation

S.M.G. Cioffi
Primo
;
D. Galimberti
;
C. Fenoglio;M. Serpente;M. Arcaro;E. Scarpini
Penultimo
;
2016

Abstract

Mutations in progranulin gene (GRN) are a common cause of autosomal dominant frontotemporal lobar degeneration syndromes and are associated with a wide phenotypic heterogeneity. The majority of genetic defects in GRN consists of loss-of-function mutations, causing haploinsufficiency, and is associated with extremely low plasma progranulin levels. Herein, we describe a patient who developed language dysfunctions and memory disturbances at 63 years of age. Considering the early onset and the positive family history (sister aged 50 with non-fluent/agrammatic variant of primary progressive aphasia, father with behavioral disturbances in his sixties), a genetic analysis was carried out, showing the presence of a novel mutation [g.9543delA (IVS3-2delA)] in a predicted splicing site of GRN. Her progranulin plasma levels were under the reference threshold, as in her sister, thus supporting the causative role of the new variant. The same genetic mutation was confirmed by sequencing in her sister. Results described enlarge current knowledge on genetic causes of the disease and clinical characteristics of carriers.
deletion; frontotemporal dementia; haploinsufficiency; mutation; non-fluent variant primary progressive aphasia; progranulin (grn); splicing; clinical psychology; geriatrics and gerontology; psychiatry and mental health
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/502877
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