Genetic contributions to sporadic frontotemporal dementia

Carr, Jessie S.; Sirkis, Daniel W.; Yokoyama, Jennifer S.

doi:10.1016/b978-0-12-815868-5.00005-0

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…Recent estimates indicate that most cases of FTD are sporadic (55–75%), whereas the remaining 25–55% of cases are familial, in which mutations in three main genes have been documented: chromosome 9 open reading frame 72 ( C9ORF72 ), microtubule associated protein tau ( MAPT ), and progranulin ( GRN ) [ 54 ]. These mutations give rise to a high heterogeneity of clinical and neuropathological manifestations with varying degrees of frontal and temporal lobe neuronal loss, atrophy, gliosis, and protein accumulation [ 55 ]. Specifically, MAPT mutations mainly determine the deposition of the microtubule-associated protein tau, whereas C9ORF72 mutations determine the transactive response (TAR) DNA-binding protein of 43 kDa (TDP43).…”

Section: Calabria As a Genetic Isolate For Neurodegenerative Diseasesmentioning

confidence: 99%

Calabria as a Genetic Isolate: A Model for the Study of Neurodegenerative Diseases

Bruno

Laganà²,

Lorenzo³

et al. 2022

Biomedicines

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Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology—ranging from clinical activity to the genealogical reconstruction of families/populations across the centuries, the creation of databases, and molecular/genetic research—was modelled on the characteristics of the Calabrian population for more than three decades. This methodology allowed the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, a higher prevalence of several hereditary neurodegenerative diseases has been reported in this population, such as Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, Niemann–Pick type C disease, spinocerebellar ataxia, Creutzfeldt–Jakob disease, and Gerstmann–Straussler–Scheinker disease. Here, we summarize and discuss the results of research data supporting the view that Calabria could be considered as a genetic isolate and could represent a model, a sort of outdoor laboratory—similar to very few places in the world—useful for the advancement of knowledge on neurodegenerative diseases.

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Section: Calabria As a Genetic Isolate For Neurodegenerative Diseasesmentioning

confidence: 99%

Calabria as a Genetic Isolate: A Model for the Study of Neurodegenerative Diseases

Bruno

Laganà²,

Lorenzo³

et al. 2022

Biomedicines

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“…Based on clinical presentation, it can be classified into: (i) behavioral variant FTD (bvFTD); (ii) non-fluent primary progressive aphasia (PPA); (iii) and semantic variant primary progressive aphasia (svPPA) [46]. Recent estimates indicate that most cases of FTD are sporadic (55-75%) whereas the remaining 25-55% of cases are familial in which mutations in three main genes have been documented: chromosome 9 open reading frame 72 (C9ORF72), microtubule associated protein tau (MAPT) and progranulin (GRN) [47]. These mutations give rise to a high heterogeneity of clinical and neuropathological manifestations with a varying degrees of frontal and temporal lobe neuronal loss, atrophy, gliosis and proteins accumulation [48].…”

Section: Frontotemporal Dementiamentioning

confidence: 99%

Calabria as a Genetic Isolate, a Model for the Study of Neurodegenerative Diseases

Bruno¹,

Laganà²,

Lorenzo³

et al. 2022

Preprint

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Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with a low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology ranging from clinical activity to genealogical reconstruction of families/populations along the centuries, creation of databases, and molecular/genetic research, has been modelled on the characteristics of the Calabrian population for more than three decades. This methodology allows to the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, in this population it has been reported a higher prevalence of several hereditary neurodegenerative diseases such as Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Niemann Pick type C disease, Spino-cerebellar ataxia, Creutzfeldt–Jakob disease and Gerstmann Straussler Scheincker disease. Thus, Calabria constitutes a model for the study of neurodegenerative diseases, a sort of "outdoor laboratory" useful for the advancement of knowledge in this field. Here, we summarize and discuss some results of research data supporting the view that Calabria is a genetic isolate and could represent a useful model for the study and characterization of neurodegenerative diseases.

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“…The genetic influence of FTD is greater than in the case of AD. Between 15 and 30% of FTD cases are due to mutations in the C9orf72, GRN or MAPT genes, among others [9]. A pathogenic expansion of a hexanucleotide (G 4 C 2 ) repeat in the regulatory region of C9orf72 was recently identified as a major cause of the disease amyotrophic lateral sclerosis and frontotemporal dementia10.…”

Section: Introductionmentioning

confidence: 99%

Early-Onset Alzheimer’s Disease, APOE4 And C9orf72 Expansion: A Case Report

2024

Ann Case Report

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Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease, and frontotemporal dementia (FTD) have become a focus of concern at the socio-sanitary and economic level due to their exponential growth as life expectancy for humans has increased through the years. Research into the genetic basis underlying the diseases should allow for earlier diagnosis, better prognosis and the possibility of discovering new therapeutic targets. In this article, we describe the case of a 45-year-old patient who presented with early-onset dementia with symptoms similar to AD, for which he was diagnosed. However, his genetic study revealed a mutation in C9orf72, a gene associated with FTD and amyotrophic lateral sclerosis. In addition, the patient is a heterozygous carrier of APOE c.338T>C (E4 allele), considered a risk factor for AD. This finding would suggest an involvement of C9orf72 in triggering AD.

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Genetic contributions to sporadic frontotemporal dementia

Cited by 4 publications

References 54 publications

Calabria as a Genetic Isolate: A Model for the Study of Neurodegenerative Diseases

Calabria as a Genetic Isolate: A Model for the Study of Neurodegenerative Diseases

Calabria as a Genetic Isolate, a Model for the Study of Neurodegenerative Diseases

Early-Onset Alzheimer’s Disease, APOE4 And C9orf72 Expansion: A Case Report

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