RNA Splicing Defects in Hypertrophic Cardiomyopathy: Implications for Diagnosis and Therapy

Ribeiro, Marta; Furtado, Marta; Martins, Sandra; Carvalho, Tereza Cristina de; Carmo‐Fonseca, Maria

doi:10.3390/ijms21041329

Cited by 16 publications

(6 citation statements)

References 85 publications

(107 reference statements)

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“…Splice site variants very often introduce a PTC resulting in the inactivation (loss of function/haploinsufficiency) of the mutated allele. 12,17 In the case of in-frame exon skipping, as well as for exon deletion(s) or duplication(s), an altered (shortened or lengthened) peptide is expected to be produced. It can than either be misfolded and eliminated within the cell or secreted as an altered monomer expected to affect proper microfibril assembly.…”

Section: Variants Categorizationmentioning

confidence: 99%

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

Arnaud

Hanna

Ropers

et al. 2021

Archives of Cardiovascular Diseases Supplements

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.Clinical relevance of genotype-phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

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Section: Variants Categorizationmentioning

confidence: 99%

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

Arnaud

Hanna

Ropers

et al. 2021

Archives of Cardiovascular Diseases Supplements

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“…The role of splicing in HCM is becoming an area of increased focus [ 36 ]. Proteomic analysis of primary tissue from the failing hearts of 16 HCM patients has recently revealed a common pattern of altered sarcomeric proteoforms compared with heart tissues from nonfailing donors [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of Cardiomyocyte Extracellular Vesicles in Hypertrophic Cardiomyopathy Reveals Differential snoRNA Cargo

James

Nizamudeen

Lea

et al. 2021

Stem Cells and Development

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Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness that can lead to devastating conditions such as heart failure and sudden cardiac death. Despite extensive study, the mechanisms mediating many of the associated clinical manifestations remain unknown and human models are required. To address this, human-induced pluripotent stem cell (hiPSC) lines were generated from patients with a HCM-associated mutation (c. ACTC1 G301A ) and isogenic controls created by correcting the mutation using CRISPR/Cas9 gene editing technology. Cardiomyocytes (hiPSC-CMs) were differentiated from these hiPSCs and analyzed at baseline, and at increased contractile workload (2 Hz electrical stimulation). Released extracellular vesicles (EVs) were isolated and characterized after a 24-h culture period and transcriptomic analysis performed on both hiPSC-CMs and released EVs. Transcriptomic analysis of cellular mRNA showed the HCM mutation caused differential splicing within known HCM pathways, and disrupted metabolic pathways. Analysis at increasing contraction frequency showed further disruption of metabolic gene expression, with an additive effect in the HCM background. Intriguingly, we observed differences in snoRNA cargo within HCM released EVs that specifically altered when HCM hiPSC-CMs were subjected to increased workload. These snoRNAs were predicted to have roles in post-translational modifications and alternative splicing, processes differentially regulated in HCM. As such, the snoRNAs identified in this study may unveil mechanistic insight into unexplained HCM phenotypes and offer potential future use as HCM biomarkers or as targets in future RNA-targeting therapies.

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“…Moreover, after the implantation, there is a slight inflammatory response. Patient with recurrent miscarriages and infertility develop less prominent reaction that may prevent the fetus from implantation [72][73][74].…”

Section: When Will We Check a Patient For Aplsmentioning

confidence: 99%

Antiphospholipid Syndrome and Pregnancy-Diagnosis, Complications and Management: An Overview

Tsikouras¹,

Tsiggalou²,

Bothou³

et al. 2022

Inflammation in the 21st Century

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Antiphospholipid syndrome which is also known as APS is an autoimmune disease which represents an acquired form of thrombophilia. The etiology of APS remains unknown. This disorder occurs when the immune system mistakenly attacks some of the normal human proteins and manifests itself as recurrent arterial or venous thrombosis and it could emerge after abortions or in recurrent pregnancy loss. In APS, the body produces the wrong antibodies against phospholipid-binding proteins, that is present in the blood and plays an important role in coagulation. Antibodies are specific proteins that usually target and neutralize the body’s invaders, such as viruses and bacteria. When antibodies attack phospholipid-binding proteins, blood clots abnormally. Specifically, it could cause blood clots in veins or arteries leading to stroke and various pregnancy complications such as: endometrial death, miscarriage, preeclampsia, intrauterine growth restriction and prematurity. APS is divided into primary and secondary, which is associated with autoimmune diseases and more often with systemic lupus erythematosus (SLE), while antibodies against cardiolipin are detected in many other conditions (infections, malignancies, drugs, etc.). The symptoms of APS, in addition to arterial and/or venous thrombosis and pregnancy complications, are multisystemic and the differential diagnosis of the primary APS from the secondary, in the context of SLE, is of particular clinical interest and is subject of this literature review.

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RNA Splicing Defects in Hypertrophic Cardiomyopathy: Implications for Diagnosis and Therapy

Cited by 16 publications

References 85 publications

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

Transcriptomic Analysis of Cardiomyocyte Extracellular Vesicles in Hypertrophic Cardiomyopathy Reveals Differential snoRNA Cargo

Antiphospholipid Syndrome and Pregnancy-Diagnosis, Complications and Management: An Overview

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