Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins

Maggi, Lorenzo; Mavroidis, Manolis; Psarras, Stelios; Capetanaki, Yassemi; Lattanzi, Giovanna

doi:10.3390/ijms22084256

Cited by 38 publications

(34 citation statements)

References 164 publications

(418 reference statements)

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“…Maggi et al reviewed the recent discoveries related to skeletal and cardiac muscle disorders caused by mutations in the genes DES, SYNM, and LMNA encoding for the IFs desmin, synemin, and A-type lamins, respectively [2]. Concretely, they summarized clinical and molecular features of desmin, lamin, and synemin IF-associated striated muscle disorders and suggested pathogenetic hypotheses based on the interplay of desmin and lamin A/C proteins.…”

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confidence: 99%

Recent Advances in Intermediate Filaments—Volume 1

Saéz

González-Granado

2022

IJMS

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Recent Advances in Intermediate Filaments—Volume 1

Saéz

González-Granado

2022

IJMS

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“…Filamin C (FLNC) is an important structural crosslinker of actin rods at the sarcomeric z-disc of both cardiac and skeletal muscle. Moreover, as filamin A, FLNC can serve as a nodal point for sarcomeric mechano-transduction in different muscle cells [ 50 ]. Filamin C was first reported to be associated with various forms of skeletal myopathy [ 51 ].…”

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confidence: 99%

Genetic Background and Clinical Features in Arrhythmogenic Left Ventricular Cardiomyopathy: A Systematic Review

Bariani

Rigato

Cason

et al. 2022

JCM

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In recent years a phenotypic variant of Arrhythmogenic cardiomyopathy has been described, characterized by predominant left ventricular (LV) involvement with no or minor right ventricular abnormalities, referred to as Arrhythmogenic left ventricular cardiomyopathy (ALVC). Different disease-genes have been identified in this form, such as Desmoplakin (DSP), Filamin C (FLNC), Phospholamban (PLN) and Desmin (DES). The main purpose of this critical systematic review was to assess the level of knowledge on genetic background and clinical features of ALVC. A search (updated to April 2022) was run in the PubMed, Scopus, and Web of Science electronic databases. The search terms used were “arrhythmogenic left ventricular cardiomyopathy” OR “arrhythmogenic cardiomyopathy” and “gene” OR “arrhythmogenic dysplasia” and “gene”. The most represented disease-gene turned out to be DSP, accounting for half of published cases, followed by FLNC. Overall, ECG abnormalities were reported in 58% of patients. Major ventricular arrhythmias were recorded in 26% of cases; an ICD was implanted in 29% of patients. A total of 6% of patients showed heart failure symptoms, and 15% had myocarditis-like episodes. DSP is confirmed to be the most represented disease-gene in ALVC patients. An analysis of reported clinical features of ALVC patients show an important degree of electrical instability, which frequently required an ICD implant. Moreover, myocarditis-like episodes are common.

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“…Desminopathies become manifest clinically as different cardiomyopathies and/or skeletal myopathies [1,2]. The clinical spectrum of desminopathies is wide and heterogenous and includes different skeletal myopathies and cardiomyopathies like dilated (DCM) [3][4][5], arrhythmogenic (ACM) [6,7], hypertrophic (HCM) [8,9], restrictive (RCM) [10,11] or non-compaction cardiomyopathy (NCCM) [12,13].…”

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confidence: 99%

The N-terminal Part of the 1A Domain of Desmin Is a Hot Spot Region for Putative Pathogenic DES Mutations Affecting the Filament Assembly

Brodehl¹,

Holler²,

Gummert³

et al. 2022

Preprint

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Desmin is the major intermediate filament protein of all three muscle cell types and connects different cell organelles and multi-protein complexes like the cardiac desmosomes. Several pathogenic mutations in the DES gene cause different skeletal and cardiac myopathies. However, the significance of the majority of DES missense variants is currently unknown since functional data are lacking. To determine whether desmin missense mutations within the highly conserved 1A coil domain cause a filament assembly defect, we generated a set of variants with unknown significance and analyzed systematically the filament assembly in transfected SW13 and H9c2 cells using confocal microscopy. We found that mutations in the N-terminal part of the 1A coil domain affect the filament assembly leading to the cytoplasmic desmin aggregation. In contrast, mutant desmin in the C-terminal part of the 1A coil domain form filamentous structures comparable to wild-type desmin. Our findings suggest that the N-terminal part of the 1A coil domain is a hot spot for pathogenic desmin mutations, which affect the desmin filament assembly leading in consequence to skeletal and/or cardiac myopathies. This study may have relevance for the genetic counselling of patients carrying variants in the 1A coil domain of the DES gene.

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Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins

Cited by 38 publications

References 164 publications

Recent Advances in Intermediate Filaments—Volume 1

Recent Advances in Intermediate Filaments—Volume 1

Genetic Background and Clinical Features in Arrhythmogenic Left Ventricular Cardiomyopathy: A Systematic Review

The N-terminal Part of the 1A Domain of Desmin Is a Hot Spot Region for Putative Pathogenic DES Mutations Affecting the Filament Assembly

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