Among patients with hypertrophic cardiomyopathy (CMH) in whom they identified mutations in the MYL2 (160781) and MYL3 (160790) genes (see MOLECULAR GENETICS section), Poetter et al. (1996) observed unusual mid-left ventricular chamber thickening apparent in the left ventriculogram ... Among patients with hypertrophic cardiomyopathy (CMH) in whom they identified mutations in the MYL2 (160781) and MYL3 (160790) genes (see MOLECULAR GENETICS section), Poetter et al. (1996) observed unusual mid-left ventricular chamber thickening apparent in the left ventriculogram and associated with a pressure gradient detectable by Doppler echocardiography. Massive hypertrophy of the cardiac papillary muscles and adjacent ventricular tissue was present, causing a midcavitary obstruction. Flavigny et al. (1998) studied 42 probands from unrelated families with familial hypertrophic cardiomyopathy and identified 2 new mutations in the MYL2 gene in 3 probands. These mutations were subsequently found in all affected family members, who were classified morphologically as Maron type 1, 2, or 3; none had the variant phenotype described by Poetter et al. (1996). Kabaeva et al. (2002) described 2 unrelated families with CMH, each having a different heterozygous missense mutation in MYL2 and a distinct phenotype. Affected members of 1 family had mild to moderate septal hypertrophy, a late onset of clinical manifestations, and a benign disease course and prognosis. The proband from the other family had first been diagnosed at age 7 years with nonobstructive myocardial hypertrophy and underwent implantation of a cardioverter defibrillator at age 25 years after ventricular tachycardia degenerating into ventricular fibrillation was observed. She had recurrent episodes of supraventricular tachycardia, and echocardiography revealed asymmetric septal hypertrophy. DNA was not available from her sister, who had asymmetric obstructive myocardial hypertrophy and died suddenly at the age of 21 years, or from her father, who died unexpectedly at a young age and was found to have myocardial hypertrophy on autopsy. The mutation was not found in the proband's mother, who had normal cardiac findings.
In 4 patients with a variant form of CMH involving mid-left ventricular chamber hypertrophy, Poetter et al. (1996) identified heterozygous mutations in the MYL2 and the MYL3 genes. Three mutations were found in MYL2: ala13 to thr (A13T; ... In 4 patients with a variant form of CMH involving mid-left ventricular chamber hypertrophy, Poetter et al. (1996) identified heterozygous mutations in the MYL2 and the MYL3 genes. Three mutations were found in MYL2: ala13 to thr (A13T; 160781.0001), glu22 to lys (E22K; 160781.0002), and pro94 to arg (P94R; 160781.0003). Three patients from 2 unrelated families had the E22K mutation. In these individuals, as well as the individual with the A13T mutation, the cardiac morphology was strikingly similar to that seen in patients with MYL3 mutations (e.g., 160790.0001) in that pronounced midcavitary obstruction was present. Flavigny et al. (1998) screened 42 probands from unrelated families with CMH for mutations in the MYL2 gene and identified 2 novel mutations, arg58 to gln (R58Q; 160781.0004) and phe18 to leu (F18L; 160781.0005). None of the affected individuals had the variant form of CMH described by Poetter et al. (1996). Kabaeva et al. (2002) analyzed the MYL2 and MYL3 genes in 186 unrelated individuals with CMH and identified 2 missense mutations in MYL2: E22K and R58Q. The former was associated with a more benign phenotype and the latter with a more severe one of asymmetric septal hypertrophic cardiomyopathy.