A unique common ancestor introduced P301L mutation in MAPT gene in frontotemporal dementia patients from Barcelona (Baix Llobregat, Spain)

2019 ◽  
Vol 84 ◽  
pp. 236.e9-236.e15 ◽  
Author(s):  
Leire Palencia-Madrid ◽  
Raquel Sánchez-Valle ◽  
Ierai Fernández de Retana ◽  
Sergi Borrego ◽  
Oriol Grau-Rivera ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Common Ancestor ◽  
Dementia Patients ◽  
Mapt Gene ◽  
P301l Mutation

Frequency of common genetic forms of frontotemporal dementia in a Russian cohort of patients

2020 ◽  
pp. 30-32
Author(s):  
Ю.А. Шпилюкова ◽  
Е.Ю. Федотова ◽  
Н.Ю. Абрамычева ◽  
С.Н. Иллариошкин
Keyword(s):  
Frontotemporal Dementia ◽  
Clinical Phenotypes ◽  
Mapt Gene ◽  
First Time

Впервые в российской популяции на когорте пациентов с клиническим диагнозом ЛВД исследована частота встречаемости мутаций в наиболее частых генах, ассоциированных с данным заболеванием. Наибольшая часто мутирующими являются гены C9orf72 и GRN. Реже всего встречаются мутации в гене MAPT, что возможно связано с неравномерным представительством клинических фенотипов в нашей выборке. For the first time in the Russian cohort of FTD patients the frequency of mutations in the most common genes associated with this disease was studied. The most frequently mutating are the genes C9orf72 and GRN. Mutations in the MAPT gene are least likely to occur, which is probably due to the uneven representation of clinical phenotypes in our sample.

Frontotemporal dementia-related gene mutations in clinical dementia patients from a Chinese population

2016 ◽  
Vol 61 (12) ◽  
pp. 1003-1008 ◽  
Author(s):  
Zhihong Shi ◽  
Shuai Liu ◽  
Lei Xiang ◽  
Ying Wang ◽  
Mengyuan Liu ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Chinese Population ◽  
Gene Mutations ◽  
Related Gene ◽  
Dementia Patients

scholarly journals Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162592 ◽  
Author(s):  
Gamze Guven ◽  
Ebba Lohmann ◽  
Jose Bras ◽  
J. Raphael Gibbs ◽  
Hakan Gurvit ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Mutation Frequency ◽  
Dementia Patients

Frontotemporal Dementia Phenotype Associated with MAPT Gene Duplication

2010 ◽  
Vol 21 (3) ◽  
pp. 897-902 ◽  
Author(s):  
Anne Rovelet-Lecrux ◽  
Didier Hannequin ◽  
Olivier Guillin ◽  
Solenn Legallic ◽  
Snejana Jurici ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Frontotemporal Dementia ◽  
Mapt Gene

scholarly journals Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrew E. Arrant ◽  
Jonathan R. Roth ◽  
Nicholas R. Boyle ◽  
Shreya N. Kashyap ◽  
Madelyn Q. Hoffmann ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Posttranslational Modifications ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Inferior Frontal Gyrus ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Metabolizing Enzymes ◽  
Dementia Patients ◽  
The Brain

AbstractLoss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia. Most pathogenic GRN mutations result in progranulin haploinsufficiency, which is thought to cause frontotemporal dementia in GRN mutation carriers. Progranulin haploinsufficiency may drive frontotemporal dementia pathogenesis by disrupting lysosomal function, as patients with GRN mutations on both alleles develop the lysosomal storage disorder neuronal ceroid lipofuscinosis, and frontotemporal dementia patients with GRN mutations (FTD-GRN) also accumulate lipofuscin. The specific lysosomal deficits caused by progranulin insufficiency remain unclear, but emerging data indicate that progranulin insufficiency may impair lysosomal sphingolipid-metabolizing enzymes. We investigated the effects of progranulin insufficiency on sphingolipid-metabolizing enzymes in the inferior frontal gyrus of FTD-GRN patients using fluorogenic activity assays, biochemical profiling of enzyme levels and posttranslational modifications, and quantitative neuropathology. Of the enzymes studied, only β-glucocerebrosidase exhibited impairment in FTD-GRN patients. Brains from FTD-GRN patients had lower activity than controls, which was associated with lower levels of mature β-glucocerebrosidase protein and accumulation of insoluble, incompletely glycosylated β-glucocerebrosidase. Immunostaining revealed loss of neuronal β-glucocerebrosidase in FTD-GRN patients. To investigate the effects of progranulin insufficiency on β-glucocerebrosidase outside of the context of neurodegeneration, we investigated β-glucocerebrosidase activity in progranulin-insufficient mice. Brains from Grn−/− mice had lower β-glucocerebrosidase activity than wild-type littermates, which was corrected by AAV-progranulin gene therapy. These data show that progranulin insufficiency impairs β-glucocerebrosidase activity in the brain. This effect is strongest in neurons and may be caused by impaired β-glucocerebrosidase processing.

scholarly journals P4-664: A PHASE 1 STUDY OF AL001 IN HEALTHY VOLUNTEERS AND FRONTOTEMPORAL DEMENTIA PATIENTS CARRYING A GRANULIN MUTATION

2019 ◽  
Vol 15 ◽  
pp. P1585-P1586
Author(s):  
Robert Paul ◽  
Michael Ward ◽  
Omer Siddiqui ◽  
Mackenzie Hagey ◽  
Hua Long ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Frontotemporal Dementia ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Dementia Patients

scholarly journals Anosognosia in Early- and Late-Onset Dementia and Its Association With Neuropsychiatric Symptoms

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuela Tondelli ◽  
Chiara Galli ◽  
Giulia Vinceti ◽  
Luigi Fiondella ◽  
Simone Salemme ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Disease Progression ◽  
Frontotemporal Dementia ◽  
Late Onset ◽  
Neuropsychiatric Symptoms ◽  
Diagnostic Delay ◽  
Early Onset Dementia ◽  
Dementia Patients ◽  
Clinical Variants ◽  
Late Onset Dementia

Background: The symptom anosognosia or unawareness of disease in dementia has mainly been studied in patients with late-onset dementia (LOD, ≥65 years), whereas little is known on whether it is also present in patients with early-onset dementia (EOD, <65 years). We aimed at investigating differences in anosognosia between LOD and EOD, by also studying its association with different clinical variants of EOD and the presence of neuropsychiatric symptoms.Methods: A total of 148 patients, 91 EOD and 57 LOD, were recruited and underwent extended clinical assessment and caregiver interview that included questionnaires aimed at measuring anosognosia and neuropsychiatric symptoms. Differences in anosognosia between EOD and LOD and between subgroups with different clinical variants were investigated, as well as correlation between anosognosia and neuropsychiatric symptoms. A regression analysis was applied to explore the association between anosognosia and development of neuropsychiatric symptoms during disease progression.Results: Median levels of anosognosia were not significantly different between EOD and LOD. Anosognosia increased overtime with disease progression and was higher in frontotemporal dementia patients or, more precisely, in frontotemporal dementia and Alzheimer's disease variants associated with involvement of the frontal lobes. Higher levels of early anosognosia were associated with higher frequency and severity of subsequent neuropsychiatric symptoms, in particular apathy, later in the course of the disease.Conclusion: Anosognosia is a frequent symptom of EOD, occurring in 94.5% of all-cause EOD, and it is associated with higher risk of developing neuropsychiatric symptoms during disease progression. Recognising anosognosia may be helpful for clinicians and families to reduce diagnostic delay and improve disease managment.

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