目的研究国人肥厚型心肌病（HCM）患者的致病基因～肌球蛋白结合蛋白c基因（myosin binding protein C gene，MYBPC3）的突变位点，分析基因突变类型与临床表型的相互关系。方法对66例HCM患者的MYBPC3基因进行扫描，聚合酶链反应扩增其外显子及剪接部位的基因组DNA片段，直接测序分析。分析各突变患者相应的临床表型特点。结果经测序分析，发现Lys301fs移码突变、Asp463stop无义突变、Gly523Arg错义突变和Tyr847His错义突变。MYBPC3导致的HCM为3例，占病例总数的4．5％。其临床表型各异，患者H30（Lys301fs）47岁发病，活动后胸闷、气短，超声显示室间隔肥厚达18．7mm，左心室后壁14．7mm。患者H48（Asp463stop）为25岁男性，24岁发病，室间隔肥厚达15．4mm。患者H53（Gly523Arg和Tyr847His）发病年龄36岁，活动后胸闷、憋气，伴心前区疼痛，室间隔肥厚达27mm。结论MYBPC3突变为HCM主要致病原因之一。MYBPC3突变基因携带者临床表型差异大。国人MYBPC3突变患者多在青壮年期发病，不同于国外报道的多发病较晚。
OBJECTIVE: To investigate whether direct administration of adenoviral vectors (Ad) containing the complementary deoxyribonucleic acid (cDNA) of vascular endothelial growth factor 165 (Ad-VEGF165) induces porcine coronary collateral vessel formation, improves regional myocardial perfusion and function and is safe. METHODS: Three weeks after miniature swine underwent left thoracotomy and placement of an Ameroid constrictor on the left circumflex coronary artery (LCX), Ad-VEGF165 (n = 6) or the control, Ad expressing beta-galactosidase cDNA (Ad-Gal, n = 6), was directly administered into the ischemic myocardium in the circumflex distribution. All animals were sacrificed 4 wk after the second surgery. Myocardial perfusion and function were assessed by electrocardiogram-gated single photon emission computed tomography (GSPECT) imaging. Ex vivo coronary angiography was performed to examine collateral vessels. Toxicity was assessed by blood analyses on the day just before (day 0) and on day 1, 3, 7, 28 after vector delivery and by vascular, myocardial and liver histology after sacrifice. RESULTS: GSPECT imaging 4 wk after administration of Ad-VEGF165 demonstrated significant reduction in ischemic area (P
