遗传性球形红细胞增多症患者的临床及遗传学分析  

Clinical and genetics features of patients with hereditary spherocytosis

作　　者：孟庆杰 邬欢 郭伟娜 沈芯 向贇[1] Meng Qingjie;Wu Huan;Guo Weina;Shen Xin;Xiang Yun(Clinical laboratory,Wuhan Children′s Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan 430016,China)

机构地区：[1]华中科技大学同济医学院附属武汉儿童医院检验科,武汉430016

出　　处：《中华检验医学杂志》2024年第5期543-547,共5页Chinese Journal of Laboratory Medicine

基　　金：湖北省自然科学基金(2023AFB893)。

摘　　要：目的:探讨遗传性球形红细胞增多症(Hereditary spherocytosis,HS)患者临床及遗传学特点,报道发现的新突变位点。方法:回顾性分析2017年6月1日至2023年1月31日在武汉儿童医院就诊的35例HS患儿的临床资料,其中24例男孩,11例女孩,年龄7.8(4.0,9.9)岁,分析其临床、血常规及生化检测等实验室结果,利用高通量测序技术对纳入患儿进行致病基因检测,不同基因型之间血液学参数采用Mann-Whitney U检验进行数据分析。结果:35例患者临床表现为贫血;33例患儿存在黄疸、28例患儿脾大,11例患儿合并胆石症;35例患儿的基因检测结果均为阳性,17例患儿携带ANK1基因突变,14例患儿携带SPTB基因突变,1例患儿携带SPTA1基因突变,1例患儿携带SLC4A1基因突变;其中2例患儿同时携带ANK1和SPTB基因突变;35例患儿中共检测出39个突变位点,根据ACMG指南分为27个致病变异,6个可能致病变异,6个临床意义未明变异;所有变异位点中8个为已报道突变,31个为未见报道的新突变;携带ANK1变异的患儿与携带SPTB变异的患儿相比,外周血红细胞数量、血红蛋白含量、网织红细胞计数等差异均无统计学意义(P均>0.05)。结论:HS患儿致病基因突变以ANK1和SPTB突变为主,携带其2种基因型的患儿之间表型无明显差异;并报道了31个新突变,扩展了该类疾病的变异谱。Objective To investigate the clinical features and characteristics of gene mutation of patients with Hereditary spherocytosis(HS)and report novel mutations found in this work.Method We reviewed the literatures for the clinical and genetic features of the 35 patients(24 boys and 11 girls,median age 7.8 years)with HS admitted to Wuhan Children′s Hospital from June 2017 to January 2023.Analyze clinical manifestations the blood routine,and biochemical laboratory results,and use Next-generation sequencing(NGS)to detect pathogenic mutation.Mann-Whitney U testing method was used to analyze the hematological parameters between different genotypes.Results All of the patients showed clinical manifestations of anemia;33 children had jaundice,28 children had splenomegaly,and 11 children had gallstones.Gene mutations were detected in all 35 patients.17 patients carried ANK1 variants,14 patients harbored SPTB variants,1 patient carried SPTA1variants,1 patient carried SLC4A1 variants,and 2 patients harbored both ANK1 and SPTB variants.A total of 39 heterozygous mutations were found,among which 27 were pathogenic,6 was likely pathogenic and 6 were of unknown significance according to the ACMG guideline;Among 39 mutations identified,31 were novel.There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the ANK1 mutant group and the SPTB group(all P>0.05).Conclusion SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hubei,China,and there was no significant difference in phenotype between ANK1 and SPTB genotype.We found 31 unreported novel variants and expanded the spectrum of variation in this type of disease.

关 键 词：红细胞增多症 遗传性球形红细胞增多症 NGS测序 临床表型 基因突变 

分 类 号：R555.1[医药卫生—血液循环系统疾病]