To find more genetic variation to extend knowledge of mutations in MYH7 gene linked to skeletal muscle disorders.

Genotype-phenotype relationship regarding the effect of mutation in MYH7 gene affecting slow/cardiac beta myosin heavy chain (MyHCI) is complex. Questions regarding why some mutations cause cardiomyopathy or skeletal muscle disorders alone or combination of both still need to be answered. More findings in genetic variation would extend knowledge of mutations in MYH7 gene linked to skeletal muscle disorders.

We present a female adult patient with a new phenotypic variant of childhood onset of muscular disorders and predominant involvement of thigh muscles with biopsy showing intrasarcoplasmic inclusion bodies. Whole exome sequencing showed that variant c.1370T>G (p.Ile457Arg) in the MYH7 gene is a missense mutation possibly linked to the clinical findings. The amino acid sequence affected by this mutation would be in highly conserved central 50-kDa cleft of myosin motor domain.

Given this mutation is located within motor domain of MyHCI, this might affect at some point the regulation of myosin mechano-chemical activity during the contractile cycle. Consequently, this potentially damaging effect can be easily amplified within the network of ~300-myosin molecules forming thick filament and therefore become additively deleterious, affecting in turn the overall organization and performance of sarcomere.