Myosin Heavy Chain ۷ Plays An Important Role inMyocardial Wall Development

Objective: Cardiomyopathy is a pathologic condition which isassociated with ventricular wall dysfunction. Left ventricularnoncompaction (LVNC) was primarily classified as an inheritedcardiomyopathy. Although several reports have been publishedabout this disease, but the genetic basis is not fully elucidated yet.Materials and Methods: Using whole-exome sequencing(WES), we inves tigated a family with several affected membersexhibiting LVNC phenotype. Bioinformatics analysis identifieda candidate variation which was checked in all family membersusing Sanger sequencing. The candidate pathogenic variationwas examined for expression pattern, protein sequence, andmutant domains in different organisms. In silico prediction ofthree-dimensional (۳D) s tructure of native and mutant type ofcandidate variant was done to analyze the effect of mutation onprotein s tructure and function.Results: We identified a novel heterozygous missense variant(c.۱۹۶۳C>A:p.Leu۶۵۵Met) in the gene encoding myosin heavychain ۷ (MYH۷) with autosomal dominant inheritance. Thisgene is evolutionary conserved among different organisms.We identified MYH۷ as a highly enriched isoform, comparedto other types of myosin heavy chains, in skeletal and cardiacmuscles. Furthermore, Myh۷ was among a few isoforms ofMyh in mouse heart that highly expresses from early embryonicto adult s tages. In silico predictions showed an altered actinmyosinbinding, resulting in weaker binding energy that cancause LVNC.Conclusion: A novel mutation c.۱۹۶۳C>A:p.Leu۶۵۵Met inMYH۷ with autosomal dominant inheritance was associatedwith LVNC. Determining the genotype of the gene in all membersof this family could help in early diagnosis of the diseaseand PGD of the next generation.

کلیدواژه ها:

Left Ventricular Noncompaction (LVNC) ، MyosinHeavy Chain ۷ (MYH۷) ، Whole-Exome Sequencing (WES) ، Protein Modeling