A missense mutation in the beta-myosin heavy chain gene in a Japanese patient with hypertrophic cardiomyopathy.

A 55-year-old man had been previously admitted at the age of 44 because of chest pain on effort. He was diagnosed as hypertrophic obstructive cardiomyopathy with a left ventricular outflow pressure gradient of 65 mmHg. We analyzed the cardiac beta-myosin heavy chain gene in this patient using polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP analysis). PCR-SSCP analysis revealed a sequence variation within exon 16. A G-to-A transversion with replacement of Val by Met at codon 606 was confirmed by sequencing analysis. Previously, a 606Val-->Met mutation has been reported to give a benign prognosis because of the neutral charge substitution. However, there have been some premature deaths in this patient's kindred. Thus, despite the absence of a change in charge, this mutation may be malignant in some kindreds.