A frameshift deletion mutation in the cardiac myosin-binding protein C gene associated with dilated phase of hypertrophic cardiomyopathy and dilated cardiomyopathy.
A frameshift deletion mutation in the cardiac myosin-binding protein C gene associated with dilated phase of hypertrophic cardiomyopathy and dilated cardiomyopathy.
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DOI：
10.1016/j.jjcc.2010.04.003
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发表时间：
2010-09
影响因子：
2.5
通讯作者：
N. Hitomi;T. Kubo;H. Kitaoka;Takayoshi Hirota;T. Hamada;Eri Hoshikawa;Kayo Hayato;M. Okawa;A. Kimura;Y. Doi
中科院分区：
文献类型：
--
作者：
N. Hitomi;T. Kubo;H. Kitaoka;Takayoshi Hirota;T. Hamada;Eri Hoshikawa;Kayo Hayato;M. Okawa;A. Kimura;Y. Doi
然而，很少有研究报道心肌肌球蛋白结合蛋白C（MyBPC）基因的某些突变与类似扩张型心肌病（DCM）的肥厚型心肌病（D-HCM）扩张期相关。我们研究了5个不相关的心肌病先证者，这些先证者是由MyBPC基因的相同突变引起的。方法对176例HCM先证者中的4例和54例DCM先证者中的1例进行MyBPC基因的检测，发现18，535和18，536位核苷酸有2个碱基缺失，即R945 fs/105突变。对这些先证者亲属的遗传分析显示，还有一名成员具有这种突变。共有6例受试者发生R945 fs/105突变。这6例患者诊断时的平均年龄为61岁。在最初的评估中，其中三人被诊断为HCM与正常的左心室（LV）收缩功能。另外两名患者已经患有D-HCM。其余1例患者因左室收缩功能降低（射血分数=31%）而无左室壁厚度增加而被诊断为DCM。在随访期间（7.6年），所有3例左心室收缩功能受损的患者均因心力衰竭和/或持续性室性心动过速而入院治疗。最后，1例诊断为D-HCM的患者死于心力衰竭. CONCLUSIONSSThe患者与此突变可能会发展LV收缩功能障碍，并遭受心血管事件，通过中年及以后。
OBJECTIVESA few studies reported that some mutations in the cardiac myosin-binding protein C (MyBPC) gene were associated with dilated phase of hypertrophic cardiomyopathy (D-HCM) resembling dilated cardiomyopathy (DCM). We studied 5 unrelated cardiomyopathy probands caused by an identical mutation in the MyBPC gene. The results of clinical and genetic investigations in these patients are presented in this paper.METHODSWe analyzed MyBPC gene in DCM patients as well as patients with HCM.RESULTSAn R945fs/105 mutation, 2-base deletion at nucleotides 18,535 and 18,536, was identified in 4 of the 176 HCM probands and in 1 of the 54 DCM probands. Genetic analysis in relatives of those probands revealed another one member with this mutation. A total of 6 subjects had R945fs/105 mutation. The mean age of these six patients at diagnosis was 61 years. At initial evaluation, three of them were diagnosed as having HCM with normal left ventricular (LV) systolic function. The other two patients already had D-HCM. The remaining one patient was diagnosed as having DCM because of reduced LV systolic function (ejection fraction=31%) without increased LV wall thickness. During follow-up (7.6 years), all three patients with impaired LV systolic function were admitted for treatment of heart failure and/or sustained ventricular tachycardia. Finally, one patient with the diagnosis of D-HCM died of heart failure.CONCLUSIONSThe patients with this mutation may develop LV systolic dysfunction and suffer from cardiovascular events through mid-life and beyond.