PRKAG2心脏综合征患者心肌肥厚的治疗

Treatment of myocardial hypertrophy in patients with PRKAG2 cardiac syndrome

目的调查一个存在PRKAG2心脏综合征(一种由编码腺昔酸激活的蛋白激酶γ2亚基的PRKAG2基因突变导致的疾病)的中国汉族5代家系,分析其中伴有心肌肥厚患者的治疗。方法本研究以完全房室传导阻滞伴室间隔非对称性肥厚为主要表现的一个中国汉族5代大家系(n=40)为研究对象,提取可获得的30名家庭成员(6例患者和24例正常人)外周血DNA。应用目的基因捕获结合高通量测序技术对该家系成员进行基因检测。在明确基因诊断后,以室间隔厚度的平均年增加率(以mm/年表示)为指标,对该家系中服用P受体阻滞剂患者的心脏资料进行回顾性分析。结果家系中共6例患者携带PRKAG2基因(c.905G>A;pR302Q)杂合变异。家系患者表型以完全房室传导阻滞伴非对称性室间隔肥厚为主要特征,同质性高,植入心脏永久起搏器后无再发晕厥,但有房扑、房颤的发生。5例患者长期服用B受体阻滞剂,心肌肥厚进展显著延缓。结论当患者出现完全房室传导阻滞伴非对称性室间隔肥厚时,应考虑PRKAG2突变的可能。心脏起搏器的及时植入以及β受体阻滞剂的长期服用可改善预后。

Objective To investigate a 5-generation Chinese Han family with PRKAG2 cardiac syndrome resulting from mutations in the PRKAG2 gene encoding the AMP-activated protein kinase(AMPK)gamma 2 subunit and the treatment of myocardial hypertrophy in patients with PRKAG2 cardiac syndrome.Method In this study,a 5-generation Chinese Han family(n=40)with complete atrioventricular block and asymmetric interventricular septal hypertrophy was taken as the research object,and the DNA were obtained from 30 of them(6 patients and 24 normal persons).Objective gene capture combined with high-throughput sequencing technique was used to detect the genes of family members.After the gene diagnosis was confirmed,the cardiac data of patients taking beta-blockers in this family were analyzed retrospectively with the average annual increase in thickness of interventricular septum(expressed in mm/year)as an index.Results A total of 6 family members were associated with PRKAG2(c.905G>A;pR302Q)heterozygous variation.The phenotype of pedigree patients is characterized by complete atrioventricular block and asymmetric interventricular septal hypertrophy;which has high homogeneity;No syncope occurs after implantation of permanent pacemaker;but atrial flutter and atrial fibrillation occur The 5 patients with PRKAG2 cardiac syndrome in the family took beta-blockers for a long time,and the progress of cardiac hypertrophy was significantly delayed.Conclusions Our results suggest that the possibility of PRKAG2 mutations should be considered in patients with complete atrioventricular block and asymmetric interventricular septal hypertrophy^and that prompt implantation of pacemakers and long-term use of beta blockers may improve the prognosis of PRKAG2 cardiac syndrome patients。