26例遗传性球形红细胞增多症的临床及基因诊断  

Clinical and genetic diagnosis for 26 paitents with hereditary spherocytosis

作　　者：白丽红[1] 郑丽萍 李彬媛 黄惠 施小六[2] 易彦[1] BAI Lihong;ZHENG Liping;LI Binyuan;HUANG Hui;SHI Xiaoliu;YI Yan(Department of Hematology,Second Xiangya Hospital,Central South University,Changsha 410011;Department of Medical Genetics,Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]中南大学湘雅二医院血液内科,长沙410011 [2]中南大学湘雅二医院医学遗传科,长沙410011

出　　处：《中南大学学报（医学版）》2023年第4期565-574,共10页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(2019JJ50869,2018JJ2562)。

摘　　要：目的:遗传性球形红细胞增多症(hereditary spherocytosis,HS)是最常见的遗传性红细胞膜缺陷病,主要表现为贫血、黄疸、脾大。由于部分患者临床表现不典型、家族史阴性,加上传统的实验室检查敏感性和特异性均较低,常导致漏诊、误诊。目前已明确ANK1、SPTB、SPTA1、SLC4A1和EPB42基因突变可引起其对应的编码蛋白质缺失,进而导致红细胞膜缺陷。本研究旨在分析HS基因诊断的可行性和临床应用价值。方法:回顾性收集2018年1月至2021年9月中南大学湘雅二医院血液内科收治的26例中国湖南HS患者的资料,分析其临床表现和实验室检测结果。应用二代测序(next-generation sequencing,NGS)结合Sanger测序,检测HS致病基因突变和胆红素代谢调控关键酶尿苷二磷酸葡萄糖醛酸转移酶1家族多肽A1(uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1,UGT1A1)变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)发布的《序列变异解释的标准和指南》进行致病基因变异判读。分析不同基因变异类型患者的临床特征,并对其临床诊断和基因诊断进行对比分析。结果:在26例HS患者中,贫血23例、黄疸25例、脾大24例、胆石症14例;16例有家族史,10例无家族史;25例HS致病基因突变检测结果为阳性,1例阴性。19个家系共检出18个HS致病基因杂合变异,其中14个为致病性变异,1个可能致病性变异,3个意义未明变异。SPTB突变(12个)和ANK1突变(4个)最多。变异类型以无义突变为主(9个)。SPTB突变组与ANK1突变组相比,外周血红细胞参数及溶血指标的差异均无统计学意义(均P>0.05)。ANK1突变组切脾率高于SPTB突变组,差异有统计学意义(χ^(2)=6.970,P=0.014)。不同突变类型(无义突变、移码突变、剪接位点突变及错义突变)组间外周血红细胞参数及溶血指标差异亦均无统计学意义(均P>0.05)。临床确�cell membrane,mainly characterized by anemia,jaundice,and splenomegaly.Due to the atypical clinical manifestations and negative family history of some patients,as well as the low sensitivity and specificity of traditional laboratory examinations,it is easy for it to escape diagnosis or be misdiagnosed.At present,it has been confirmed that the mutation of ANK1,SPTB,SPTA1,SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins,and thus lead to the defect of erythrocyte membrane.This study aims to analyze the feasibility and clinical application value of HS gene diagnosis.Methods:Data of 26 patients from Hunan,China with HS admitted to the Department of Hematology,Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected,and their clinical manifestations and results of laboratory examinations were analyzed.Next-generation sequencing(NGS)combined with Sanger sequencing were applied.The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1(UGT1A1),a key enzyme in the regulation of bilirubin metabolism,were detected.The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics(ACMG).The clinical characteristics of patients with different gene variants were analyzed,and the clinical diagnosis and genetic diagnosis were compared.Results:Among the 26 patients with HS,there were 23 cases of anemia,25 cases of jaundice,24 cases of splenomegaly,and 14 cases of cholelithiasis.There were 16 cases with family history and 10 cases without family history.The results of HS mutation test were positive in 25 cases and negative in 1 case.A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families,among which 14 were pathogenic,1 was likely pathogenic and 3 were of unknown

关 键 词：遗传性球形红细胞增多症 临床表型 二代测序 基因型 基因诊断 尿苷二磷酸葡萄糖醛酸转移酶1家族多肽A1 

分 类 号：R556.6[医药卫生—血液循环系统疾病]