Clinical characterization of Idiopathic Restrictive Cardiomyopathy having rare variant (E949K) in β-cardiac myosin heavy chain gene

Kapoor, Mitali; Biswas, Amitabh; Das, Soumi; Seth, Sandeep; Bhargava, Balram; Rao, Vadlamudi Raghavendra

doi:10.1186/1755-8166-7-s1-p34

Cited by 2 publications

(2 citation statements)

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“…Mutations in contractile proteins such as α-actin, troponin I, and troponin T have been identified as causative of RCM [3–6]. Cardiac β myosin heavy chain gene mutations were also recently linked to RCM in newborns [7,8] and children [9]. Furthermore, some myosin mutations that cause hypertrophic cardiomyopathy (HCM) with minimal left ventricular hypertrophy also produce a restrictive phenotype, suggesting a continuum between the HCM and RCM classifications, with RCM often considered an extreme form of HCM [10,11].…”

Section: Introductionmentioning

confidence: 99%

A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila

Achal

Trujillo

Melkani

et al. 2016

Journal of Molecular Biology

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An “invariant proline” separates the myosin S1 head from its S2 tail and is proposed to be critical for orienting S1 during its interaction with actin, a process that leads to muscle contraction. Mutation of the invariant proline to leucine (P838L) caused dominant restrictive cardiomyopathy in a pediatric patient (Karam et al., Congenit. Heart Dis. 3:138–43, 2008). Here, we use Drosophila melanogaster to model this mutation and dissect its effects on the biochemical and biophysical properties of myosin, as well as on the structure and physiology of skeletal and cardiac muscles. P838L mutant myosin isolated from indirect flight muscles of transgenic Drosophila showed elevated ATPase and actin sliding velocity in vitro. Furthermore, the mutant heads exhibited increased rotational flexibility, and there was an increase in the average angle between the two heads. Indirect flight muscle myofibril assembly was minimally affected in mutant homozygotes, and isolated fibers displayed normal mechanical properties. However, myofibrils degraded during aging, correlating with reduced flight abilities. In contrast, hearts from homozygotes and heterozygotes showed normal morphology, myofibrillar arrays, and contractile parameters. When P838L was placed in trans to Mhc5, an allele known to cause cardiac restriction in flies, it did not yield the constricted phenotype. Overall, our studies suggest that increased rotational flexibility of myosin S1 enhances myosin ATPase and actin sliding. Moreover, instability of P838L myofibrils leads to decreased function during aging of Drosophila skeletal muscle, but not cardiac muscle, despite the strong evolutionary conservation of the P838 residue.

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Section: Introductionmentioning

confidence: 99%

A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila

Achal

Trujillo

Melkani

et al. 2016

Journal of Molecular Biology

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“…These cardiomyopathy hallmarks have also been confirmed in our mutation carriers. Several studies have shown an association of sequence variant rs121913629 with the different phenotypes and their heterogeneity [17][18][19][20]. A large portion of patients harbors multiple sequence variants.…”

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confidence: 99%

Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients

Zigová

Bernasovská

Boroňová

et al. 2017

Clinical Laboratory Analysis

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In our study, we identified known and novel sequence variants in 23 unrelated patients with hypertrophic cardiomyopathy, but we did not observe any strong mutation hotspot. The results of our study assumed that exon 23 of MYH7 gene can be in potential affinity to hypertrophic cardiomyopathy in our cohort of patients. The sequence variants identified in this study may be further investigated in order to determine their functions in disease pathogenesis and improve management, diagnosis, and treatment in Slovak patients.

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Clinical characterization of Idiopathic Restrictive Cardiomyopathy having rare variant (E949K) in β-cardiac myosin heavy chain gene

Cited by 2 publications

References 0 publications

A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila

A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila

Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients

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