[一个因基因拷贝数变异缺失导致遗传性球形红细胞增多症的中国家系的基因分析]
[Genetic Analysis of a Chinese Pedigree with Hereditary Spherocytosis Caused by Copy Number Variation Deletion of Gene].
作者信息
Chen Xiang-Lei, Li Jing-Gang, Men Qian, Li Xin
机构信息
Department of Hematology, Yidu Central Hospital of Weifang, Weifang 262500, Shandong Province, China.E-mail:
Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
出版信息
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Feb;31(1):183-188. doi: 10.19746/j.cnki.issn.1009-2137.2023.01.029.
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-qPCR was used to detect the relative mRNA levels of candidate gene. The structure and function of SPTB protein were analyzed by UniProt and SMART databases.
RESULTS
We infer that the gene copy number variation (CNV) deletion was co-segregated with the phenotype of the patients in this family based on the results of second-generation sequencing (about 700 target genes). The UCSC Genome Browser demonstrated that the deleted region was mainly located in exon2-3 of gene. The results of RT-qPCR showed that the relative mRNA levels of all patients were lower than the healthy control. UniProt 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 gene may be the reason for the hereditary spherocytosis in this family.
目的
基于对一个遗传性球形红细胞增多症家系的临床特征和基因突变分析，探讨该疾病的分子机制。
方法
2021年5月，一名患有黄疸和贫血的先证者被转诊至潍坊益都中心医院。采集了该家系6名成员的外周血样本。采用二代测序技术筛选致病突变，并挑选出具有临床意义的变异位点。随后利用相关数据库对变异位点进行分析，采用RT-qPCR检测候选基因的相对mRNA水平。通过UniProt和SMART数据库分析SPTB蛋白的结构和功能。
结果
基于二代测序（约700个靶基因）结果，我们推断该家系中患者的基因拷贝数变异（CNV）缺失与患者表型共分离。UCSC基因组浏览器显示，缺失区域主要位于基因的外显子2-3。RT-qPCR结果显示，所有患者的相对mRNA水平均低于健康对照。UniProt和SMART数据库分析表明，不含CH1和CH2结构域的SPTB蛋白无法与红细胞膜肌动蛋白结合。
结论
基因的CNV缺失可能是该家系遗传性球形红细胞增多症的病因。
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