Frequency of frontotemporal dementia-related gene variants in Turkey

Artan, Sevilhan; Gökalp, Ebru Erzurumluoğlu; Samancı, Bedia; Adapınar, Demet Özbabalık; Bas, Hasan; Tepgeç, Fatih; Ekenel, Emilia Qomi; Çilingir, Oğuz; Bılgıç, Başar; Gürvıt, Hakan; Hanağası, Haşmet; Kocagil, Sinem; Aras, Beyhan Durak; Uyguner, Oya; Emre, Murat

doi:10.1016/j.neurobiolaging.2021.05.007

Cited by 4 publications

(2 citation statements)

References 73 publications

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“…To date, two c‐truncating mutations in CHMP2B have been associated with FTD in a single Danish family (c.532‐1A>T), and a patient with familial FTD(c.493C>T) has been reported from Belgium (Skibinski et al, 2005 ; van der Zee et al, 2008 ). In addition, four missense mutations of CHMP2B associated with FTD has been reported in Europe (c.442G>T), France (c.581C>T), the United States (g.26218C>T), and Türkiye (c.389A>G) (Artan et al, 2021 ; Ferrari et al, 2010 ; Ghanim et al, 2010 ; Skibinski et al, 2005 ), resulting in amino acid changes. However, the mechanism of their functional impact on CHMP2B remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Several large‐scale studies on FTLD patients have failed to detect any CHMP2B mutations (Cannon et al, 2006 ; Momeni et al, 2006 ; Rizzu et al, 2006 ), which is in accordance with previous studies in China (Shi et al, 2016 ). To date, CHMP2B C‐truncating mutations associated with FTD have been described in a single family from Denmark andone individual with familial FTD from Belgium (Skibinski et al, 2005 ; van der Zee et al, 2008 ); three CHMP2B missense mutations have also been reported in France, the United States, and Türkiye (Artan et al, 2021 ; Ferrari et al, 2010 ; Ghanim et al, 2010 ). The current study identified a novel CHMP2B variant and summarized the genetic and phenotypic characteristics of the proband in the Chinese population.…”

Section: Introductionmentioning

confidence: 99%

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A novel splice‐site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review

Wen

Zhao³

et al. 2023

Molec Gen & Gen Med

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BackgroundFrontotemporal dementia (FTD) has genetic heterogeneity, and the endosomal ESCRTIII‐complex subunit CHMP2B variant is a rare cause of FTD. The mutations in CHMP2B were first identified in a large Danish pedigree with autosomal dominant FTD, and have also been found in several individuals from Belgium, France, the United States, and Türkiye. In the Chinese population, cases of CHMP2B variant‐associated FTD have never been reported.MethodsThe spectrum of clinical symptoms and the genetic analysis of the presented patient were identified and investigated. Besides this case, we assessed previously reported cases with CHMP2B gene mutations.ResultsThis study presents a Chinese patient harboring a novel heterozygous A‐to‐T variant (NM_014043:c.532‐2A>T) in CHMP2B with a phenotype compatible with FTD. Although previous reports suggested cases of CHMP2B variant‐associated FTD initially presented with personality changes and stereotypical movements at the age of 50, this case was characterized by psychosis involving delusion of persecution, auditory hallucination, and suspiciousness at the earlier onset age of 44. Minigene splicing assay revealed that the splice‐site variant could result in the retention of intron 5.ConclusionThis is the first case of CHMP2B variant‐associated FTD reported in the Chinese population. The novel c.532‐2A>T variant in the acceptor splice site of exon 6 retaining intron 5 was predicted to cause truncated protein and protein conformation changes. This discovery may expand the genetic and phenotypic spectrum of CHMP2B variant‐associated FTD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel splice‐site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review

Wen

Zhao³

et al. 2023

Molec Gen & Gen Med

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Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research

Nuytemans,

Franzen,

Broce

et al. 2024

Alzheimer's & Dementia

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Frontotemporal dementia (FTD) is one of the leading causes of young‐onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross‐cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.

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Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review

Villa,

Pellencin,

Romeo

et al. 2024

Front. Biosci. (Landmark Ed)

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Background: Microtubule-associated protein tau (MAPT) mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity. A behavioural variant of FTD is the principal phenotype, but other rarer phenotypes are described, mostly reported as single cases. In this review, we provide an overview of the clinical phenotypes associated with MAPT mutations in order to define their characteristics and explore genotype-phenotype correlations. Methods: We performed systematic bibliographic research on the Pubmed database, focusing on articles published between 1998 and 2022. We analysed the clinical phenotype of 177 patients carrying MAPT mutations, focusing on the rarest ones. We performed a narrative synthesis of the results. Results: Regarding language phenotypes, the most frequent were the non-fluent variant and the semantic variant of Primary Progressive Aphasia (nfvPPA, svPPA), approximately in the same proportion. Almost 20% of the whole group of patients present a clinical phenotype belonging to the corticobasal syndrome-progressive supranuclear palsy (CBS-PSP) spectrum. While no clear genotype-phenotype correlation could be identified, some mutations were associated with a specific phenotype, while others gave origin to multiple clinical pictures and mixed phenotypes. Conclusions: A high clinical heterogeneity exists in FTD associated with MAPT mutations without a clear phenotype-genotype correlation in most cases. However, some characteristics can be helpful to drive genetic testing. Deep phenotyping of patients, together with functional studies of single mutations, particularly those associated with atypical phenotypes, are necessary to better understand the biological mechanisms underlying this clinical variability.

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Frequency of frontotemporal dementia-related gene variants in Turkey

Cited by 4 publications

References 73 publications

A novel splice‐site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review

A novel splice‐site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research

Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review

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