Myh2 encodes MyHCIIa, a myosin heavy chain present in fast type 2A fibers. It is crucial for muscle function, and its associated pathways likely involve muscle contraction and development. Genetic models, such as KO/CKO mouse models, can be valuable for studying its function [1,2,3,4,5].

Pathogenic variants in MYH2 have been implicated in various myopathies, including dominant and recessive forms. These myopathies present with features like slowly progressive, predominantly proximal myopathy, chronic progressive external ophthalmoplegia (CPEO), muscle weakness, and in some cases, esophageal reflux, proptosis, and unique muscle MRI findings. Some variants affect splicing, resulting in novel transcripts [1,2,3]. In one case, a neonate with a MYH2 mutation showed hypotonia, dysmorphic features, dysphagia, and aspiration, along with decreased type 2A fibers and vacuoles in muscle biopsy [4]. An adult patient with MYH2-myopathy caused by two heterozygous pathogenic variants had a novel myopathological phenotype including centralized large myofilamentous tangles associated with nemaline rods and ring fibers [5].

In conclusion, Myh2 is essential for normal muscle function, and its malfunction due to genetic variants leads to various myopathies. Studies on Myh2, especially through genetic models, contribute to understanding the molecular mechanisms of these myopathies, which may potentially guide future diagnostic and therapeutic strategies for muscle-related diseases.