目的 对3例儿童Rotor综合征的临床特点及SLCO1B1和SLCO1B3基因突变分析,提高儿科医生对Rotor综合征的认识。方法 收集广州市妇女儿童医疗中心2018年—2019年确诊的3例Rotor综合征患儿的临床资料,对患儿及其家系成员肝脏常见遗传代谢性疾病二代测序筛查并家系验证结果进行分析。结果 患儿主要临床表现为反复或持续巩膜和(或)皮肤轻度黄染,实验室检查提示高直接胆红素血症。二代测序发现3例患儿均为SLCO1B1基因c.1738C＞T纯合突变和SLCO1B3基因5号内含子区域大片段插入纯合突变。SLCO1B1基因和SLCO1B3基因2处纯合突变均进行了家系验证。文献报道的SLCO1B1基因c.1738C＞T突变是无义突变,可以造成蛋白功能缺失;SLCO1B3基因的大片段插入突变虽暂未有文献收录或报道,但大片段的插入突变可引起移码突变而造成编码蛋白功能丧失。结论 由于基因检测技术的不断进步,Rotor综合征不断被儿科医生所认识。SLCO1B1和SLCO1B3双基因纯合或复合杂合突变是3例Rotor综合征患儿的分子遗传基础。

Objective To better understand Rotor syndrome(RS)in children,the clinical features and SLCO1B1 and SLC01B3 gene mutations were analyzed. Methods The clinical data of the 3 pediatric cases diagnosed in Guangzhou Women and Children's Medical Center between 2018 and 2019 was collected. Genomic DNA was extracted from the children and their family members, and subjected for second-generation sequencing to screen the known genes for liver genetic metabolic diseases. Then the detected mutations were confirmed by Sanger sequencing analysis. Results The main clinical manifestations were recurrent or persistent mild yellowish sclera and/or skin. Laboratory examinations showed hyperbilirubinemia with direct bilirubin elevating. Second generation sequencing showed that all 3 children were c.1738c＞Thomozygous mutations of SLCO1B1 gene and homozygous mutations of large fragment insertion in SLCO1B3 gene intron 5. Two homozygous mutations in SLCO1B1 gene and SLCO1B3 gene were verified in families.SLCO1B1 gene c.1738C＞T mutation,a nonsense mutation reported in references,could lead to protein function loss.A large insertion mutation of SLCO1B3 gene could cause frame-shift mutation which might lead to protein function loss even though it was neither reported in the references nor recorded in SNP database. Conclusion Due to the progress in the clinical application of gene detection technology, RS has been recognized gradually by pediatricians. Homozygous mutations or compound heterozygous mutations simultaneously occurred in SLCO1B1 and SLCO1B3 gene were the molecular genetics base in these cases of RS.

目的 探讨MDS、MDS/AML及原发AML基因突变频谱的异同点及其临床意义。方法 选取98例MDS患者、32例MDS/AML患者及234例原发AML患者为研究对象,利用二代测序技术检测基因突变。结果 MDS组中突变率较高的基因突变为TET2(16.7%,16/96)、U2AF1(12.0%,6/50)、SF3B1(11.8%,9/76);MDS/AML组中突变率较高的基因突变为TP53(33.3%,2/6)、DNMT3A(30%,6/20)、IDH2(21.1%,4/19);原发AML组中突变率较高的基因突变为FLT3-ITD(18.0%,42/233)、NPM1(16.3%,38/233)、DNMT3A(14.9%,14/94)。DNMT3A(P=0.006)、IDH2(P=0.004)及NPM1(P=0.002)等基因突变在MDS与MDS/AML两组间的突变率有统计学差异;FLT3-ITD(P=0.001)、NPM1(P=0.002)、CEBPA(P=0.011)及IDH2(P=0.019)等基因突变在MDS与原发AML两组间的突变率有统计学差异;所有受检基因突变在MDS/AML与原发AML两组间的基因突变的突变率无统计学差异(P＞0.05)。结论 MDS、MDS/AML及原发AML基因突变的突变频谱具有相似性及异质性,从MDS到MDS/AML、原发AML基因突变的变化不仅影响疾病转归及预后而且可帮助鉴别MDS/AML和原发AML。

Objective To explore the similarities and differences of spectrum of gene mutations in patients with myelodysplastic syndrome, MDS/AML and de novo acute myeloid leukemia and their clinical significance. Methods 98 patients with MDS, 32 patients with MDS/AML, 234 patients with de novo AML were selected. Gene mutations were detected by second generation sequencing. Results The most frequent mutations in MDS were as follows:TET2(16.7%, 16/96), U2AF1(12.0%, 6/50), SF3B1(11.8%, 9/76); The most frequent mutations in MDS/AML were TP53(33.3%, 2/6), DNMT3A(30%, 6/20), IDH2 (21.1%, 4/19);The most frequent mutations in de novo AML were FLT3-ITD(18.0%, 42/233), NPM1(16.3%, 38/233), DNMT3A(14.9%, 14/94); DNMT3A(P=0.006),IDH2(P=0.004) and NPM1(P=0.002) were statistical difference between MDS and MDS/AML; FLT3-ITD(P=0.001),NPM1(P=0.002),CEBPA(P=0.011) and IDH2(P=0.019) were statistical difference between MDS and de novo AML;There were no siatistical significance (P>0.05) in the frequency of all detected gene mutations between MDS/AML and AML. Conclusion The spectrum of gene mutation of MDS, MDS/AML and primary AML have similarities and heterogeneity.The changes of gene mutations from MDS to MDS/AML and de novo AML not only affect disease outcome and prognosis, but also help to identify MDS/AML and de novo AML.

目的 研究EGFR基因突变与系列肿瘤标志物在160例原发性肺癌患者及51例肺部良性占位病变患者中的表达状况,为肺部占位病变的诊断、鉴别诊断和治疗提供参考依据。方法 160例肺癌患者取新鲜病理组织标本,采用扩增阻滞突变系统荧光PCR(ARMS-PCR)技术检测EGER基因突变;160例肺癌患者和51例良性占位病变患者取外周静脉血用化学发光法检测系列肿瘤标志物,用χ²检验统计分析数据。结果 160例肺癌病例中,EGFR基因野生型比率为47.56%(78/164),EGFR基因突变型比率为52.44%(86/164),突变型中21L858R点突变占23.17%(38/164),19Del缺失突变占22.56%(37/164)。肺癌组中系列肿瘤标志物较良性占位组具显著高表达,P＜0.01。差异有统计学意义。结论 肺癌致病与EGFR基因突变、肿瘤标志物高表达有显著正相关,通过肿瘤标志物和EGFR基因突变检测,结合影像学检查,将有助于肺部占位病变诊断和鉴别诊断,并为治疗手段选择提供参考依据。

Objective To research EGFR gene mutation and series of tumor markers expression in 160 patients with primary lung cancer and 51 patients with lung benign placeholder lesions, provide some references for the diagnosis, differential diagnosis and treatment in lung placeholder lesions. Methods We took fresh pathological tissue specimens from 160 cases of patients with lung cancer, Then used ARMS PCR technique to detect EGER gene mutations. We took the peripheral venous blood in 160 patients with lung cancer and 51 patients with lung benign placeholder lesions, with chemiluminescence method to detect series of tumor markers,and used thechi-square test to statistic and analysis data. Results In 160 cases of lung cancer patients,The EGFR gene wild type rate was 47.56%(78/164).The EGFR gene mutation type rate was 52.44%(86/164).In EGFR gene mutation type,The proportion of 21L858R mutation was 23.17%(38/164),19del mutation was 22.56%(37/164). Series of tumor markers had significantly higher expression in lung cancer group than in benign placeholder lesions group. P＜0.01.The difference was statistically significant. Conclusion Lung cancer pathogenesis and EGFR gene mutations, tumor markers high expression was significantly positive correlation. Through a series of tumor markers and EGFR mutation testing, combined with imaging examination, it will contribute to the diagnosis and differential diagnosis in lung placeholder lesions, and provide the basis for treatment.