BACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal lobar degeneration with tau-negative and ubiquitin-positive neuronal inclusions. Most previous studies aimed at characterizing the clinical and neuropsychological phenotype of PGRN mutation carriers included patients with different PGRN mutations, assuming that the common proposed pathogenetic mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent. RESULTS: Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients. CONCLUSIONS: Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.
BACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal lobar degeneration with tau-negative and ubiquitin-positive neuronal inclusions. Most previous studies aimed at characterizing the clinical and neuropsychological phenotype of PGRN mutation carriers included patients with different PGRN mutations, assuming that the common proposed pathogenetic mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent. RESULTS:Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients. CONCLUSIONS:Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.
Authors: Tomasz Gabryelewicz; Mario Masellis; Mariusz Berdynski; Juan M Bilbao; Ekaterina Rogaeva; Peter St George-Hyslop; Anna Barczak; Krzysztof Czyzewski; Maria Barcikowska; Zbigniew Wszolek; Sandra E Black; Cezary Zekanowski Journal: J Alzheimers Dis Date: 2010 Impact factor: 4.472
Authors: Francesco Panza; Bruno P Imbimbo; Madia Lozupone; Davide Seripa; Antonio Daniele; Mark Watling; Gianluigi Giannelli Journal: Nat Rev Neurol Date: 2020-03-23 Impact factor: 42.937
Authors: Eliana Marisa Ramos; Deepika Reddy Dokuru; Victoria Van Berlo; Kevin Wojta; Qing Wang; Alden Y Huang; Zachary A Miller; Anna M Karydas; Eileen H Bigio; Emily Rogalski; Sandra Weintraub; Benjamin Rader; Bruce L Miller; Maria Luisa Gorno-Tempini; Marek-Marsel Mesulam; Giovanni Coppola Journal: Alzheimers Dement Date: 2019-01-25 Impact factor: 21.566