ClinVar

Davis et al. (2001) identified a double point mutation in the MYLK2 gene on the maternal haplotype in a 13-year-old white male proband with early midventricular hypertrophic cardiomyopathy (see 192600). The MYLK2 mutations were ala87 to val (A87V) and ala95 to glu (A95E; 606566.0002). The proband also inherited a glu743-to-asp mutation (E743D; 160760.0024) in the beta-myosin gene (160760) from his father. Although the son had significant disease at an early age, the father and mother came to medical attention only after the diagnosis of the son. Echocardiographic evaluation showed that both parents had similarly abnormal asymmetrically thickened hearts. Although the kindred was too small for linkage analysis, kinetic studies revealed that the mutant MYLK2 had a V(max) almost double that of wildtype MYLK2, which the authors suggested may stimulate cardiac hypertrophy. Davis et al. (2001) concluded that the increased severity of the disease at such a young age in the proband suggests a compound effect.