2种新的中国人β-地中海贫血基因突变类型CD13/14(-C)和beta nt1582(A>G)突变

摘要

目的:报道2种新的中国人β-地中海贫血(β-thalassemias,β-地贫)基因突变类型CD13/14(-C)和beta nt1582(A>G)突变.方法:疑似β-地贫患者10例,其中7例为临床疑似轻型β-地贫基因携带者,1例为临床疑似重型β-地贫患者,2例为父母双方均为β-地贫基因携带者的胎儿.应用聚合酶链反应联合反向点杂交技术(PCR-RDB),以及基于PCR技术的DNA测序技术检测β血红蛋白基因.根据患者表型和以往文献报道,对新发现的基因突变性质进行分析.结果:检测出2种β-地贫常见基因突变型,分别是IVS-2-654(C>T)和-28(A>G).检测出5种β-地贫稀有基因突变型,分别是beta nt1582(A>G),PolyA(AATAAA>GATAAA);CD13/14(-C);beta nt 1586(A>G),PolyA(AATAAA>AATAGA);IVS-1-1(G>T);IVS-2-2(-T);其中前2种为新发现的β-地贫基因突变类型.结论:发现了2种新的β-地贫基因突变类型,其表型效果可能为β0或β+.对常规基因检测技术不能诊断的β-地贫疑似病例,可作DNA测序进行确诊.%Objective: To identify two novel β-thalassemia gene mutations in Chinese patients: CD13/14 (-C) and beta nt1582 (A>G), PolyA (AATAAA>GATAAA). Methods: Ten suspected cases were selected in the prenatal diagnosis center for further diagnosing β-thalassemia. Among them, 7 cases were suspected as β-thalassemia trait, 1 case was suspected as β-thalassemia major, and 2 cases were fetus whose parents were β-thalassemia gene carriers. The samples were determined by using polymerase chain reaction and reverse dot blot hybridization (PCR-RDB) techniques, and β-hemoglobin direct genomic sequencing (DGS). Results: Two types of common β-thalassemia gene mutations were detected with PCR-RDB in 3 patients and 1 fetus, which were IVS-2-654 (C>T) and-28 (A>G). Five types of rare β-thalassemia gene mutations were detected with DGS in 6 patients and 1 fetus. Among these 5 rare gene mutations, 2 novel gene mutations had been found, which were beta nt 1582 (A>G), PolyA(AATAAA>GATAAA) and CD 13/14(-C). Conclusion: Two novel β-thalassemia gene muta-tions were detected, which phenotype would be β+ or β0. If a suspected case couldn't be identified by PCR-RDB, DNA sequencing should be used for further investigation.