Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, N...Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function. Here, we collected a BBS pedigree with four members and performed whole-exome sequencing on the proband. The variants were analyzed and evaluated to confirm their pathogenicity. We found compound heterozygous variants(c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants. We also found a missense variant(c.2029G>C, p.E677Q) in NPHP1 and a missense variant(c.2470C>T, p.R824C) in BBS9 in the proband only, which are variants of uncertain significance. The compound heterozygous variants were probably responsible for the BBS phenotype in this Chinese pedigree and the missense mutations in NPHP1 and BBS9 might contribute to the mutation load.展开更多
文摘目的探讨急性心肌梗死(acute myocardial infarction,AMI)患者血浆前蛋白转化枯草杆菌蛋白酶9(PCSK9)水平对临床不良事件发生的预测价值。方法选取2017年1月~2018年12月在延安大学附属医院确诊的急性心肌梗死患者271例,平均年龄55.1±9.9岁,其中男性172例(63.47%),按出院后第1月、3月、6月、12月进行随访,随访1年,主要随访方式为电话随访和门诊随访,记录临床不良事件。共59例发生临床不良事件(21.77%)。ROC曲线结果显示:血浆PCSK9诊断AMI患者临床不良事件的最佳预测值为309.6ng/ml(曲线下面积、敏感度和特异度分别为0.773,0.779和0.746),据此将研究对象分为PCSK9(L)组(PCSK<309.6ng/ml),共163例,平均年龄55.1±9.4岁,男性102例;PCSK9(H)组(PCSK≥309.6ng/ml),共108例,平均年龄54.9±10.6岁,男性70例。比较PCSK9(H)组和PCSK9(L)组患者实验室指标血浆PCSK9、血清总胆固醇(TCHO)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血糖(GLU)、年龄、性别、既往史(吸烟、饮酒、糖尿病、高血压、高脂血症、冠心病)、入院时Killip心功能分级、左心射血分数及临床不良事件发生率。Cox回归分析血浆PCSK9水平对AMI患者临床不良事件的预测价值。结果PCSK9(H)组和PCSK9(L)组血浆PCSK9水平为386±70.31ng/ml vs 232±53.17ng/ml,差异有统计学意义(t=24.545,P=0.000),血清LDL-C水平为2.71±0.62mmol/L vs 2.19±0.57mmol/L,差异有统计学意义(t=3.616,P=0.037)。PCSK9(H)组和PCSK9(L)组复合心血管不良事件发生率为23.15%vs 11.66%,差异有统计学意义(χ^2=6.308,P=0.012),心力衰竭发生率为13.89%vs 5.52%,差异有统计学意义(χ^2=5.634,P=0.018)。经Log Rank检验:PCSK9(H)组和PCSK9(L)组非复合心血管事件生存率组间差异有统计学意义(χ^2=12.735,P=0.007)。经多因素Cox回归分析,血浆PCSK9水平是AMI患者复合心血管不良事件及心力衰竭的独立危险因素(HR=1.507~1.517,95%CI:1.218~1.735,均P<0.05)。结论血浆PCSK9水平是AMI患者临床不良心血管事件的独立危险因素。
文摘Bardet-Biedl syndrome(BBS) is a genetically heterogeneous disorder characterized by retinal dystrophy, polydactyly, obesity,developmental delay, and renal defects. At least 21 candidate BBS-associated genes(BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function. Here, we collected a BBS pedigree with four members and performed whole-exome sequencing on the proband. The variants were analyzed and evaluated to confirm their pathogenicity. We found compound heterozygous variants(c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants. We also found a missense variant(c.2029G>C, p.E677Q) in NPHP1 and a missense variant(c.2470C>T, p.R824C) in BBS9 in the proband only, which are variants of uncertain significance. The compound heterozygous variants were probably responsible for the BBS phenotype in this Chinese pedigree and the missense mutations in NPHP1 and BBS9 might contribute to the mutation load.
