Functional and Expression Studies of iPSC-Derived Cardiomyocytes Carrying a Novel HCM-Associated MYPN Genetic Variant

MYPN (c.2966A>T; p.Asn989Ile, heterozygous)

Novel heterozygous variant in MYPN (myopalladin), a sarcomeric protein binding α-actinin and nebulin; functional study on iPSC-CM demonstrating dysregulation of sarcomeric proteins and altered contractility

Identification of a novel heterozygous MYPN (myopalladin) variant in a hypertrophic cardiomyopathy patient. MYPN encodes a sarcomeric protein binding α-actinin and nebulin, with variants associated with different types of cardiomyopathies and myopathies. iPSC-cardiomyocytes generated from the patient demonstrate dysregulation of sarcomeric proteins (MYH7, TNNT2, TNNI3) and altered contractility, functionally validating the pathogenic role of the variant.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

MYPN is a lesser-known cardiomyopathy gene associated with HCM, DCM and myofibrillar myopathy. iPSC-CM functional validation is the current gold standard for variants of uncertain significance in cardiogenetics. Include in HCM panels and prioritize MYPN investigation in HCM without identified causal variant.

iPSC-CM functional study +2; novel HCM variant + sarcomeric mechanism +2; therapeutic avenue +1; Genes +1; moderate impact journal +1