遗传性球形红细胞增多症——一家系中SPTA1基因突变分析及产前诊断  

Hereditary spherocytosis——Analysis and prenatal diagnosis of SPTA1 gene mutations in a Chinese pedigree

作　　者：叶玉萍 马诗玥 廖林[1] 黄健[1] 邓雪莲 林发全[1] YE Yu-ping;MA Shi-yue;LIAO Lin;HUANG Jian;DENG Xue-lian;LIN Fa-quan(Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China;Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin 541000, China)

机构地区：[1]广西医科大学第一附属医院检验科,广西南宁530021 [2]桂林医学院附属医院检验科,广西桂林541000

出　　处：《广西大学学报（自然科学版）》2020年第4期823-828,共6页Journal of Guangxi University（Natural Science Edition）

基　　金：国家自然科学基金资助项目(81360263)。

摘　　要：对1遗传性球形红细胞增多症(HS)家系进行基因检测分析,为家系成员提供遗传咨询和产前诊断。收集家系成员的临床资料,提取家系成员外周血及羊水细胞DNA,应用蛋白免疫印迹法(Western blot)分析红细胞膜蛋白缺陷情况,用高通量测序、PCR结合Sanger测序检测分析基因突变情况。Western blot结果显示:患儿及其父亲α-血影蛋白表达量减少。高通量测序、PCR结合Sanger测序发现患儿SPTA1基因中存在c.2179_2180delAG和c.3710A>G复合杂合突变,分别来自父亲和母亲,均为新突变,其中c.2179_2180delAG为致病突变的可能性大。PCR结合Sanger测序检测胎儿羊水细胞DNA未发现其携带上述突变,胎儿娩出后随访与产前诊断结果一致。本研究发现2个SPTA1基因新突变,扩展了SPTA1基因突变谱,对HS的基因诊断和遗传咨询有重要意义。The study aims to perform genetic testing on a Chinese pedigree with hereditary spherocytosis(HS)and to provide genetic counseling and prenatal diagnosis for family members.We collected clinical data of HS pedigree,extracted peripheral blood of HS pedigree and amniotic fluid DNA of proband's mother.Western blot was performed to analyse defects of erythrocyte membrane protein.High-throughput sequencing,PCR combined with Sanger sequencing were used to detect and analyse gene mutations.Results of Western blot show that the expression ofα-spectrin in HS proband and her father decreased.And the results of high-throughput sequencing,PCR combined with Sanger sequencing demonstrate that there were c.2179_2180delAG and c.3710A>G compound heterozygous mutations in the SPTA1 gene of the proband,and they were inherited from the father and mother,respectively,both of which were novel mutations.And c.2179_2180delAG mutation may be pathogenic.PCR combined with Sanger sequencing suggests that the same mutations are not found in the fetus carried by the proband's mother who was confirmed to be healthy after birth,which is consistent with the prenatal diagnosis.This study finds two novel mutations in the SPTA1 gene and enriches the mutational spectrum of the SPTA1 gene.It is of great significance for the genetic diagnosis and genetic counseling of HS.

关 键 词：遗传性球形红细胞增多症 SPTA1基因 基因突变 α-血影蛋白 产前诊断 

分 类 号：R394[医药卫生—医学遗传学]