A novel Myosin essential light chain mutation causes hypertrophic cardiomyopathy with late onset and low expressivity.
A novel Myosin essential light chain mutation causes hypertrophic cardiomyopathy with late onset and low expressivity.
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DOI：
10.1155/2012/685108
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发表时间：
2012
影响因子：
3
通讯作者：
Christiansen M
中科院分区：
文献类型：
--
作者：
Andersen PS;Hedley PL;Page SP;Syrris P;Moolman-Smook JC;McKenna WJ;Elliott PM;Christiansen M
肥厚性心肌病(HCM)是由肌节蛋白编码基因突变引起的。编码肌球蛋白基本轻链的MYL3基因突变很少见，并与猝死有关。隐性和显性两种遗传模式都被提出。我们研究了一个因杂音而转诊的38岁无症状肥厚型心肌病男性患者的大家庭。患者行肥厚心肌病，左室肥厚(最大WT 为21 mm)，静息左室流出道梯度为36 mm Hg，左心房扩张(54 mm)。基因分型显示了MYL3中一个新的错义突变p.V79I的杂合性。在300名对照组中没有发现这种突变，患者的10个肌节基因也没有突变。级联筛查发现另外9名杂合子突变携带者，其中3人有心电图和/或超声心动图异常，但不符合肥厚型心肌炎的诊断标准。如果我们认为这个交界性HCM是P.V79I突变的表型，其外显率为40%，但非穿透性突变携带者的平均年龄为15岁，而穿透性突变携带者的平均年龄为47岁。该突变影响到一个保守的缬氨酸，在轻链和肌球蛋白杠杆臂之间的接触区域用一个更大的异亮氨酸残基取代它。综上所述，MYL3突变可以表现为低表达和起病晚。
Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a large family with a 38-year-old asymptomatic HCM-affected male referred because of a murmur. The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm). Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, in MYL3. The mutation was not found in 300 controls, and the patient had no mutations in 10 sarcomere genes. Cascade screening revealed a further nine heterozygote mutation carriers, three of whom had ECG and/or echocardiographic abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%, but the mean age of the nonpenetrant mutation carriers is 15, while the mean age of the penetrant mutation carriers is 47. The mutation affects a conserved valine replacing it with a larger isoleucine residue in the region of contact between the light chain and the myosin lever arm. In conclusion, MYL3 mutations can present with low expressivity and late onset.