Yu B, French J A, Carrier L, Jeremy R W, McTaggart D R, Nicholson M R, Hambly B, Semsarian C, Richmond D R, Schwartz K, Trent R J
Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
J Med Genet. 1998 Mar;35(3):205-10. doi: 10.1136/jmg.35.3.205.
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.
对家族性肥厚型心肌病（FHC）的DNA研究表明，该病是由构成肌肉肌节的蛋白质编码基因发生突变所致。FHC基因中的大多数突变是由错义变化引起的，不过，最近鉴定出的一个基因（心肌肌球蛋白结合蛋白C基因，MYBPC3）主要存在导致截短蛋白产生的DNA突变。已提出显性负效应和单倍体不足模型来解释FHC中的分子变化。本研究描述了两个澳大利亚家族的FHC病例，其病因是MYBPC3基因发生了不同突变。第一个家族在MYBPC3基因一个心脏特异性结构域产生了一个新生的Asn755Lys变化。第二个家族是Gln969X无义突变，导致产生截短蛋白。此前在MYBPC3基因中均未发现这两种突变。结合该疾病当前的分子模型，讨论了DNA变化对心肌肌球蛋白结合蛋白C功能的影响。
