β-地中海贫血三重突变杂合体的基因型分析

目的 对1例罕见的β-地中海贫血三重基因突变杂合子进行基因型分析.方法 采用反向点杂交和DNA测序法分析患者β-珠蛋白基因型.结果 反向点杂交结果显示,此病例β-珠蛋白基因上有转录子+40～+43、密码子41/42、IVS-2-654 3种突变.基因克隆以及DNA测序分析证实患者一条染色体上存在+40～+43(-AAAC)+CD41/42(-TCTT)复合突变;其同源染色体上存在IVS-2-654(C→T)点突变.患者基因型为+40～+43(-AAAC)·CD41/42(-TCTT)]/IVS-2-654(C→T).结论 β-地中海贫血+40～+43(-AAAC)·CD41/42(-TCTT)/N]突变基因型是我国一种新的地中海贫血突变类型.

β-thalassemia major caused by compound heterozygosity for +40 to+43(-AAAC),IVS-2-654(C to T)and codon 41/42(-TCTT)

Objective To report the analysis of a rare β-thalassemia ternary heterozygote+40 to+43(-AAAC)·CD41/42(-TTCT)·IVS-2-654]causing β-thalassemia major in a Chinese,Methods Using PCR-ASO probe hybridization analysis to scan 17 known types of beta-thalassemia mutations,and gene cloning and DNA sequencing to i- dentify the underlying causative mutation.Results Reverse dot blot (RDB)analysis showed that the patient's β-globin gene had three mutations to:+40 to+43(-AAAC),CD41/42(-TCTT)and IVS-2-654(C to T).β-globin gene cloning and sequencing proved that,the two deletions of +40 to+43(-AAAC)and CD41/42(-TCTT)co-existed on the same chromosome,and the other homologous chromosome had an IVS-2-654(C to T)mutation.So the potient is a compound heterozygote of+40 to+43(-AAAC)·CD41/42(-TCTT)]/IVS-2-654(C to T)leading to β-thalassemia major.Con-clusion The triple mutation of+40 to+43(-A AAC)·CD41/42(-TCTT)/N]is a new genotype of beta-thalassemia in Chinese.