【摘要】 目的：对一个遗传性球形红细胞增多症家系进行临床表征及基因变异分析，并探讨其发病的分子机制。方法：先证者因黄疸、贫血于2021年5月就诊于潍坊市益都中心医院，采集其家系6人外周血，采用二代测序对先证者及其家系患病成员及3名健康成员进行致病基因变异筛查，选取有临床意义的变异位点，结合有关数据库对变异位点进行分析；对候选变异基因的m RNA表达水平进行RT-q PCR分析。利用Uni Prot与SMART数据库分析SPTB蛋白的结构与功能。结果：含近700个基因的二代测序结果筛查到SPTB基因CNV缺失与该家系患者表型共分离。通过UCSC数据库分析确定该缺失区域主要位于SPTB基因exon2-3。RT-q PCR分析表明患者SPTB m RNA水平明显低于健康对照。Uni Prot与SMART数据库分析表明缺失CH1、CH2结构域的SPTB蛋白不能与红细胞膜肌动蛋白结合。结论：SPTB基因CNV缺失可能是导致该家系遗传性球形红细胞增多症的原因。更多还原

【Abstract】 Objective:To investigate the molecular mechanism of the disease based on the clinical characterization and genetic mutation analysis in a family with hereditary spherocytosis.Methods:The proband with jaundice and anemia was referred to Yidu Central Hospital of Weifang in May 2021.Peripheral blood samples were collected from six members of the family.Second-generation sequencing was used to screen the pathological mutations,and the clinically significant variant sites were selected.Then the relevant databases were used to analyze the variant sites,and RT-q PCR was used to detect the relative m RNA levels of candidate gene.The structure and function of SPTB protein were analyzed by Uni Prot and SMART databases.Results:We infer that the SPTB gene copy number variation (CNV) deletion was cosegregated with the phenotype of the patients in this family based on the results of second-generation sequencing (about700 target genes).The UCSC Genome Browser demonstrated that the deleted region was mainly located in exon2-3 of SPTB gene.The results of RT-q PCR showed that the relative SPTB m RNA levels of all patients were lower than the healthy control.Uni Prot and SMART databases analysis showed that SPTB protein without CH1 and CH2 domains could not bind to erythrocyte membrane actin.Conclusion:The CNV deletion of SPTB gene may be the reason for the hereditary spherocytosis in this family.更多还原