PT - JOURNAL ARTICLE AU - B Yu AU - J A French AU - L Carrier AU - R W Jeremy AU - D R McTaggart AU - M R Nicholson AU - B Hambly AU - C Semsarian AU - D R Richmond AU - K Schwartz AU - R J Trent TI - Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene. AID - 10.1136/jmg.35.3.205 DP - 1998 Mar 01 TA - Journal of Medical Genetics PG - 205--210 VI - 35 IP - 3 4099 - http://jmg.bmj.com/content/35/3/205.short 4100 - http://jmg.bmj.com/content/35/3/205.full SO - J Med Genet1998 Mar 01; 35 AB - DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is caused by mutations in genes coding for proteins which make up the muscle sarcomere. The majority of mutations in the FHC genes result from missense changes, although one of the most recent genes to be identified (cardiac myosin binding protein C gene, MYBPC3) has predominantly DNA mutations which produce truncated proteins. Both dominant negative and haploinsufficiency models have been proposed to explain the molecular changes in FHC. This study describes two Australian families with FHC caused by different mutations in MYBPC3. The first produces a de novo Asn755Lys change in a cardiac specific domain of MYBPC3. The second is a Gln969X nonsense mutation which results in a truncated protein. Neither mutation has previously been found in the MYBPC3 gene. The consequences of DNA changes on the function of cardiac myosin binding protein C are discussed in relation to current molecular models for this disorder.