A Miserable Phenotype of Hypertrophic Cardiomyopathy Carrying a Novel Homozygous Missense Mutation of Desmin Gene

Hypertrophic cardiomyopathy is a heterogeneous disease and many disease causing genes were identified. Most of them were sarcomeric protein and some of others were extra-sarcomeric cytoskeletons. Desmin is a member of extra-sarcomeric cytoskeletons and plays an important role of mechano-chemical network assembly in muscle cell contraction. Mutations of desmin gene provided various type of cardiomyopathy and/or general myopathy, as known in desmin-related myopathies. We identified a novel missense mutation of Thr219Pro (ACT to CCT at codon 219 located in 1B α-heical domain) in desmin gene with autosomal recessive inheritance in a twenty-year-old man. His parents who did consanguineous marriage of cousin were healthy normal with heterozygous for the mutation and wild type alleles. No familial history of cardiomyopathy was found in his family. Onset of hypertrophic cardiomyopathy was at his age of 13. Severe heart failure and arrhythmias of rapid atrial fibrillation or non-sustained ventricular tachycardia had been repeated for 4 years and left ventricular wall thickness had become thin gradually past his age of 17. General myopathy had manifested since his age of 18. Subsequently, he died suddenly after a restroom at his age of 20. We first reported a severe phenotype of hypertrophic cardiomyopathy preceding the onset of general myopathy, carrying a novel homozygous missense mutation in 1B α-helix domain of desmin gene.