Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy

Perrot, Andreas; Schmidt-Traub, Hajo; Hoffmann, Bernard; Prager, Matthias; Bit‐Avragim, Nana; Rudenko, Raisa I.; Usupbaeva, D. A.; Kabaeva, Zhyldyz; Imanov, Bakytbek; Миррахимов, М М; Witt, Heiko; Dietz, Rainer; Wycisk, Anna; Tendera, Michał; Geßner, Reinhard; Osterziel, Karl Josef

doi:10.1007/s00109-005-0722-9

Cited by 13 publications

(12 citation statements)

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“…Approximately 30% of all HCM cases are associated with variants in the MYH7 (Richard et al, ). The p.Ile736Thr MYH7 variant is a known pathogenic allele and has been reported by several studies (Barriales‐Villa et al, ; Erdmann et al, ; Perrot et al, ). Nevertheless, the p.Ile736Thr variant has also been considered a benign variant, due to its association with close to normal life expectancy (Tripathi et al, ).…”

Section: Discussionmentioning

confidence: 87%

Potential digenic inheritance of familial hypertrophic cardiomyopathy identified by whole‐exome sequencing

Ren

Chai

et al. 2020

Molec Gen & Gen Med

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Background The aim of this study was to identify the genetic causes of patients with hypertrophic cardiomyopathy (HCM) within a family. Most of the previous studies found point mutations as the genetic causes for HCM, whole‐gene deletion was rarely reported. Methods Although, clinical genetic testing has been widely used for identifying variants in HCM patients, structural variations are understudied, partly owing to the inadequacy of the available methodology. In the present study, whole‐exome sequencing (WES) and Sanger sequencing validation was used to identify the genetic causes in patients with familial HCM. Results A genomic deletion in Chromosome 19 containing the whole of troponin I3 gene (TNNI3), and the p.Ile736Thr variant in the myosin heavy chain 7 gene (MYH7) were identified in two patients with familial HCM by WES. The p.Ile736Thr variant is further validated by Sanger sequencing and is predicted as a pathogenic variant by in silico analysis. Conclusion We added the notion that not only p.Ile736Thr variant of MYH7, but also TNNI3 deletion might potentially contribute to HCM pathogenesis. Our study also suggested WES was a powerful tool to identify the genetic variants causing HCM.

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Section: Discussionmentioning

confidence: 87%

Potential digenic inheritance of familial hypertrophic cardiomyopathy identified by whole‐exome sequencing

Ren

Chai

et al. 2020

Molec Gen & Gen Med

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“…Corresponding residues in β -cardiac myosin are illustrated with our rigor state model (c) and known mutations 57-74 are listed (d). e, Table of known disease-causing mutations at the actomyosin interface 56,66,69,[74][75][76][77][78] . Numbers in parentheses give respective residue position in our published structure of NM-2C.…”

Section: Letter Researchmentioning

confidence: 99%

Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution

Ecken

Heissler

Pathan-Chhatbar

et al. 2016

Nature

219

214

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The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. The energy for these movements is generated during a complex mechanochemical reaction cycle. Crystal structures of myosin in different states have provided important structural insights into the myosin motor cycle when myosin is detached from F-actin. The difficulty of obtaining diffracting crystals, however, has prevented structure determination by crystallography of actomyosin complexes. Thus, although structural models exist of F-actin in complex with various myosins, a high-resolution structure of the F-actin–myosin complex is missing. Here, using electron cryomicroscopy, we present the structure of a human rigor actomyosin complex at an average resolution of 3.9 Å. The structure reveals details of the actomyosin interface, which is mainly stabilized by hydrophobic interactions. The negatively charged amino (N) terminus of actin interacts with a conserved basic motif in loop 2 of myosin, promoting cleft closure in myosin. Surprisingly, the overall structure of myosin is similar to rigor-like myosin structures in the absence of F-actin, indicating that F-actin binding induces only minimal conformational changes in myosin. A comparison with pre-powerstroke and intermediate (Pi-release) states of myosin allows us to discuss the general mechanism of myosin binding to F-actin. Our results serve as a strong foundation for the molecular understanding of cytoskeletal diseases, such as autosomal dominant hearing loss and diseases affecting skeletal and cardiac muscles, in particular nemaline myopathy and hypertrophic cardiomyopathy.

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“…Some describe penetrance for the whole family, while others only for adults. Some examples of general associations between genotype and penetrance are reported for MYBPC3 31 76 (late onset and higher rate of incomplete penetrance in females), MYH7 77 (age dependent penetrance), and TNNI3 (high rate of incomplete penetrance) 30. One study19 reported later penetrance in MYBPC3 families compared to MYH7 families, but another26 described a higher than expected penetrance for a MYBPC3 mutation that generated a cryptic donor splice site.…”

Section: Interventions and Prognosismentioning

confidence: 99%

A systematic review and meta-analysis of genotype–phenotype associations in patients with hypertrophic cardiomyopathy caused by sarcomeric protein mutations

Lopes

Rahman

Elliott

2013

Heart

170

105

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Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy

Abstract: Heiko Witt should have been included as the eleventh author of this paper. His affiliation is Charité

Cited by 13 publications

References 0 publications

Potential digenic inheritance of familial hypertrophic cardiomyopathy identified by whole‐exome sequencing

Potential digenic inheritance of familial hypertrophic cardiomyopathy identified by whole‐exome sequencing

Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution

A systematic review and meta-analysis of genotype–phenotype associations in patients with hypertrophic cardiomyopathy caused by sarcomeric protein mutations

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