更新于：2024-09-23
Cardiac myosin
更新于：2024-09-23
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原研机构 |
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A Phase 1, Open-label, Single-site, Randomized, Single-dose, Three-way, Crossover Study to Assess the Relative Bioavailability of BMS-986435 Tablet Formulations in Healthy Adult Participants
CAMZYOS® (Mavacamten) Post-Marketing Surveillance in Korean Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM)
一项在症状性非梗阻性肥厚型心肌病成人患者中评价Aficamten与安慰剂相比的有效性和安全性的III期、多中心、随机、双盲试验
100 项与 Cardiac myosin 相关的临床结果
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100 项与 Cardiac myosin 相关的转化医学
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2024-04-01Biochimica et biophysica acta. Molecular cell research
Missense variants in phospholamban and cardiac myosin binding protein identified in patients with a family history and clinical diagnosis of dilated cardiomyopathy
Review
作者: Lemieux, M Joanne ; Espinoza-Fonseca, L Michel ; Young, Howard S ; Armanious, Gareth P
As the genetic landscape of cardiomyopathies continues to expand, the identification of missense variants in disease-associated genes frequently leads to a classification of variant of uncertain significance (VUS). For the proper reclassification of such variants, functional characterization is an important contributor to the proper assessment of pathogenic potential. Several missense variants in the calcium transport regulatory protein phospholamban have been associated with dilated cardiomyopathy. However, >40 missense variants in this transmembrane peptide are currently known and most remain classified as VUS with little clinical information. Similarly, missense variants in cardiac myosin binding protein have been associated with hypertrophic cardiomyopathy. However, hundreds of variants are known and many have low penetrance and are often found in control populations. Herein, we focused on novel missense variants in phospholamban, an Ala15-Thr variant found in a 4-year-old female and a Pro21-Thr variant found in a 60-year-old female, both with a family history and clinical diagnosis of dilated cardiomyopathy. The patients also harbored a Val896-Met variant in cardiac myosin binding protein. The phospholamban variants caused defects in the function, phosphorylation, and dephosphorylation of this calcium transport regulatory peptide, and we classified these variants as potentially pathogenic. The variant in cardiac myosin binding protein alters the structure of the protein. While this variant has been classified as benign, it has the potential to be a low-risk susceptibility variant because of the structural change in cardiac myosin binding protein. Our studies provide new biochemical evidence for missense variants previously classified as benign or VUS.
2022-12-01Orphanet journal of rare diseases
A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy
Review
作者: Waldmüller, S ; Sperl, W ; Mayr, J A ; Landauer, F ; Bittner, R E ; Rauscher, C ; Schmidt, W M ; Freilinger, M ; Mueller-Felber, W ; Bader, Ingrid
Abstract:
Background:
Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement.
Results:
Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498_1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function.
Conclusion:
The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches.
2022-01-01Veterinary pathology2区 · 农林科学
Myocardial protein aggregates in pet guinea pigs
2区 · 农林科学
Article
作者: Kelly, Kathleen ; Southard, Teresa ; Armien, Anibal G.
A retrospective study of guinea pigs submitted for necropsy revealed intracytoplasmic inclusions in the cardiomyocytes of 26 of 30 animals. The inclusions were found with approximately the same frequency in male and female guinea pigs and were slightly more common in older animals. In most cases, the animals did not have clinical signs or necropsy findings suggestive of heart failure, and the cause of death or reason for euthanasia was attributed to concurrent disease processes. However, the 4 guinea pigs with the highest inclusion body burden all had pulmonary edema, sometimes with intra-alveolar hemosiderin-laden macrophages, suggestive of heart failure. The inclusions were found in both the left and right ventricular myocardium, mainly in the papillary muscles, but were most common in the right ventricular free wall. No inclusions were detected in the atrial myocardium or in skeletal muscle. The inclusions did not stain with Congo red or periodic acid–Schiff. Electron microscopy revealed dense aggregates of disorganized myofilaments and microtubules that displaced and compressed the adjacent organelles. By immunohistochemistry, there was some scattered immunoreactivity for desmin and actin at the periphery of the inclusions and punctate actin reactivity within the aggregates. The inclusions did not react with antibodies to ubiquitin or cardiac myosin, but were variably reactive for alpha B crystallin, a small heat shock chaperone protein. The inclusions were interpreted as evidence of impaired proteostasis.
2024-09-09
临床结果临床1期临床2期临床3期
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