Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

Liu, Yu‐Xing; Yu, Rong; Sheng, Yue; Fan, Liang‐Liang; Deng, Yao

doi:10.3389/fcvm.2022.971501

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Further genetic analysis predicted the mutation to be pathogenic, which was strengthened with its absence in 200 controls. The DES gene encodes for desmin, an intermediate filament protein that stabilizes sarcomeres and cell contacts in the cardiac intercalated disc [30]. We have little suspicion to believe that the isolated DES mutation was the causative agent for bridge development.…”

Section: Desmentioning

confidence: 99%

A Contemporary Review of the Genomic Associations of Coronary Artery Myocardial Bridging

Moore,

Murdock,

Ramanathan

et al. 2023

Genes

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Background: Myocardial bridging (MB) is a congenital coronary artery anomaly that has limited molecular disease state characterization. Though a large portion of individuals may be asymptomatic, the myocardial ischemia caused by this anomaly can lead to angina, acute coronary syndrome, coronary artery disease, and sudden cardiac death in patients. Objective: This study aims to summarize and consolidate the current literature regarding the genomic associations of myocardial bridge development and, in doing so, prompt further investigation into the molecular basis of myocardial bridge development. Methods: We performed a systematic literature review of myocardial bridging using the key search terms “Myocardial Bridging” AND (“Gene” OR “Allelic Variants” OR “Genomic”) in the databases of PubMed, CINAHL, EMBASE, and Cochran. We then performed a detailed review of the resulting abstracts and a full-text screening, summarizing these findings in this report. Results: In total, we identified eight articles discussing the associated genomics behind MB development. Studies included review articles, case reports and genomic studies that led to the discussion of several genes: DES (E434K), FBN1 (I1175M), and COMMD10; MACROD2, SLMAP, MYH7 (A1157G), and DPP6 (A714T); MYH7 (A862V); SCN2B (E31D); and NOTCH1 (R2313Q), and to the discussion of miRNAs (miR-29b, miR-151-3p, miR-126, miR-503-3p, and miR-645). Conclusions: Our study is the first to summarize the genes and molecular regulators related to myocardial bridges as they exist in the current literature. This work concludes that definitive evidence is lacking, warranting much broader genetic and genomic studies.

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Section: Desmentioning

confidence: 99%

A Contemporary Review of the Genomic Associations of Coronary Artery Myocardial Bridging

Moore,

Murdock,

Ramanathan

et al. 2023

Genes

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Mutational and clinical spectrum of myofibrillar myopathy in one center from China

Wang,

Sun,

et al. 2024

Journal of Neuromuscular Diseases

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Background: Myofibrillar myopathy (MFM) is a heterogeneous group of neuromuscular disorders characterized by degeneration of Z-disk and disintegration of myofibrils. OBJECTIVE: We aimed to analyze the mutational spectrum and phenotypic features of MFM in China. Methods: We used targeted next generation sequencing (NGS) to identify causative mutations in 39 MFM patients with confirmed myopathological diagnosis. Results: The results showed that variants were found in six MFM-associated genes, including DES, FLNC, BAG3, MYOT, TTN and DNAJB6, in 28 (71.7%), 3 (7.7%), 3 (7.7%), 1 (2.6%), 3 (7.7%), and 1 (2.6%), respectively. Of the total 26 variants identified, 19 were reported previously and 7 were novel variants. Missense variant (80.0%) was the most common mutant type of DES. P209L was the hotspot mutation of BAG3 while no obvious hotspot mutation was found of DES. Clinically, distal and proximal weakness were observed in 64.1% and 35.9% patients. Arrythmia and peripheral neuropathy were the most common combined symptoms of desminopathy and BAG3opathy, respectively. Pathologically, rimmed vacuoles (RVs) were present in different genetic type of MFM. Giant axonal nerve fiber was found in BAG3-releated MFM patient. Conlusion: We concluded that MFM showed a highly variable genetic spectrum, with DES as the most frequent causative gene followed by FLNC, BAG3 and TTN. This study expanded the genotypic and phenotypic spectrum of MFM among Chinese cohort.

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Unveiling New Insights: Reinterpreting DES Mutation, p.Arg383His, through a Study of an Iranian Family with Isolated Hypertrophic Cardiomyopathy, Implication for Phenotype‒Genotype Correlation Analysis

Kavousi,

Kamali,

Rabbani

et al. 2024

Preprint

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Background Desmin, a crucial intermediate filament in muscle cells, maintains structural integrity in cardiac muscle and provides stability to striated muscle cells. Mutations in the DES gene lead to desminopathies, causing diverse cardiac and skeletal myopathies. We examine a new Iranian family with a highly penetrant p.Arg383His variant in the DES gene, resulting in severe hypertrophic cardiomyopathy (HCM) without skeletal phenotypes. Moreover, we discuss all reported disease-causing missense variants, examining their clinical manifestations across different domains. Methods We assessed demographic data, clinical characteristics, and genetic analyses of family members. Whole genome sequencing (WGS), in silico structural and functional predictions, was also used to investigate genetic entities. A comprehensive search was performed across various databases, including to identify all disease-causing missense variants within the DES gene. Results WGS identified a p.Arg383His variant in the DES gene in the Iranian family. Analyzing 119 disease-causing missense variants in desmin revealed limited correlation between variant location and phenotypes. A significant prevalence (36.9%) of conduction diseases was linked to variants in various domains. Heart failure was associated with variants in coil2B, while syncope occurred with variants in coil2B and the tail regions. Coil1B variants showed no connection with end-stage cardiac phenotypes. Different domains showed varying associations with specific clinical outcomes, such as spine ankylosis in the tail domain and dysphonia in the desmin head domain. Conclusion The present study reports an Iranian family exhibiting severe HCM due to a novel DES gene variant, lacking skeletal myopathy phenotypes. Examining all missense variants highlighted clinical heterogeneity and complex inheritance patterns among carriers. In this context, genetic analysis is a valuable diagnostic tool for effectively managing affected patients, identifying carriers, and facilitating future family planning decisions.

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Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

Cited by 3 publications

References 24 publications

A Contemporary Review of the Genomic Associations of Coronary Artery Myocardial Bridging

A Contemporary Review of the Genomic Associations of Coronary Artery Myocardial Bridging

Mutational and clinical spectrum of myofibrillar myopathy in one center from China

Unveiling New Insights: Reinterpreting DES Mutation, p.Arg383His, through a Study of an Iranian Family with Isolated Hypertrophic Cardiomyopathy, Implication for Phenotype‒Genotype Correlation Analysis

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