Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia

@article{BermdezJimnez2018NovelDM,
  title={Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia},
  author={Francisco Jos{\'e} Berm{\'u}dez-Jim{\'e}nez and V{\'i}ctor Carriel and Andreas Brodehl and Miguel Alaminos and Antonio Campos and Ilona Schirmer and Hendrik Milting and Beatriz {\'A}lvarez Abril and Miguel A. Alvarez and Silvia L{\'o}pez-Fern{\'a}ndez and Diego Garc{\'i}a-Giustiniani and Lorenzo Monserrat and Luis Tercedor and Juan Jim{\'e}nez-J{\'a}imez},
  journal={Circulation},
  year={2018},
  volume={137},
  pages={1595–1610}
}
Background: Desmin (DES) mutations cause severe skeletal and cardiac muscle disease with heterogeneous phenotypes. Recently, DES mutations were described in patients with inherited arrhythmogenic right ventricular cardiomyopathy/dysplasia, although their cellular and molecular pathomechanisms are not precisely known. Our aim is to describe clinically and functionally the novel DES-p.Glu401Asp mutation as a cause of inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia. Methods: We… Expand
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TLDR
The genetic analysis revealed a novel small in‐frame deletion within the DES gene, p.Q113_L115del, affecting the α‐helical rod domain, classified as a pathogenic mutation associated with dilated cardiomyopathy with prominent LVHT. Expand
Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (DES) Mutation p.Y122H Leading to a Severe Filament Assembly Defect
TLDR
A small Iranian family, where the index patient received a diagnosis of restrictive cardiomyopathy (RCM) in combination with atrioventricular (AV) block, is presented, where a novel homozygous missense mutation in the DES gene (c.364T > C; p.Y122H) is revealed, which is absent in human population databases. Expand
Functional characterization of novel alpha-helical rod domain desmin (DES) pathogenic variants associated with dilated cardiomyopathy, atrioventricular block and a risk for sudden cardiac death.
TLDR
In vitro results supported the classification of DES_p.(Ile402Thr) and DES-p.(Glu410Lys) as novel pathogenic variants and demonstrated that the cardiac phenotypes associated with DES variants are diverse and cell culture experiments improve in silico analysis and genetic counseling because the pathogenicity of a variant can be clarified. Expand
The Desmin (DES) Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy
TLDR
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The novel desmin variant p.Leu115Ile is associated with a unique form of biventricular Arrhythmogenic Cardiomyopathy.
TLDR
A single desmin gene variant leads to disruption of the desmin filament network and causes a malignant biventricular form of Arrhythmogenic Cardiomyopathy, characterized by LV dysfunction and a circumferential subepicardial distribution of myocardial fibrosis. Expand
A Novel DES L115F Mutation Identified by Whole Exome Sequencing is Associated with Inherited Cardiac Conduction Disease
  • L. Hsu, Y. Ko, +5 authors G. Chang
  • Biology, Medicine
  • International journal of molecular sciences
  • 2019
Inherited cardiac conduction disease (CCD) is rare; it is caused by a large number of mutations in genes encoding cardiac ion channels and cytoskeletal proteins. Recently, whole-exome sequencing hasExpand
Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset
TLDR
A recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families and is recommended for deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. Expand
Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins
TLDR
Clinical and molecular aspects of desmin-, lamin- and synemin-related striated muscle disorders with focus on LMNA and DES-associated clinical entities are summarized and pathogenetic hypotheses based on the interplay of Desmin and lamin A/C are suggested. Expand
Arrhythmogenic Cardiomyopathy: Mechanotransduction Going Wrong
Article, see p 1595 Arrhythmogenic cardiomyopathy (AC) is a genetic disorder characterized by high risk of life-threatening ventricular arrhythmias, sudden cardiac death, and progressive heartExpand
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TLDR
The functions of desmin in health and disease with a focus on cardiomyopathies and upcoming perspectives and consequences of novel experimental approaches like genome editing technology are discussed, which might open a novel research field contributing to the development of efficient and mutation-specific treatment options. Expand
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