一种罕见的同义突变导致的β-地中海贫血的基因诊断和表型分析

Gene Diagnosis and Phenotypic Analysis ofβ-Thalassemia Caused from a Rare Synonymous Mutation CD29(C>T)

目的:对血常规和血红蛋白电泳筛查结果提示疑为β-地中海贫血携带者的孕妇及其丈夫进行β-地中海贫血基因诊断,鉴定其表型并对胎儿进行产前基因诊断。方法:采用聚合酶链式反应-反向点杂交(PCR-RDB)方法及DNA测序方法分析并鉴定孕妇及其丈夫的外周血和孕妇的羊水样本的β-珠蛋白基因突变。结果:检测到孕妇本人为常见的β-珠蛋白基因IVS-Ⅱ-654(C>T)位点杂合突变,其丈夫携带一种罕见β-珠蛋白基因CD29(c.90C>T)位点杂合突变,产前基因诊断出胎儿基因型为βIVS-Ⅱ-654/βCD29。结论:本研究在中国人群中确切基因鉴定出β-珠蛋白基因CD29(c.90 C>T)突变,此突变类型虽为同义突变但其携带者表现为β+-地中海贫血表型。考虑遗传风险应对此类同义突变给予重视,尤其对指导遗传咨询和产前基因诊断有重要意义。

Objective:To investigate the gene diagnosis and phenotypes analysis for a couple withβ-thalassemia suspected from of blood routine test and hemoglobin electrophoresis,as well as the prenatal gene diagnosis of the fetus.Methods:The gene mutation ofβ-globin in the samples of peripheral blood of pregnant woman and her husband,as well as amniotic fluid of pregnant woman were analyzied and identified by using PCR-RDB and Sanger sequencing.Results:The detection showed that the heterozygote mutation of IVS-Ⅱ-654(C>T),which is common mutation ofβ-globin gene,existed in pregnant woman,while her husband carried a rare mutation CD29(c.90 C>T)ofβ-globin gene.The prenatal diagnosis indicated that the fetus inherited with mutation from the parents,fetus genotype wasβIVS-Ⅱ-6541/βCD29.Conclusion:The CD29(C>T)mutation ofβ-globin gene has been identified in Chinese population first.Although this mutation type is symonymous mutation,but its carrier displays phenotype ofβ-thalaessmia.Therefore,the attention to this mutation should be paid considering the genetic risk.It contributes to genetic counseling and prenatal gene diagnosis.