β-地中海贫血三重突变杂合体的基因型分析

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

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—6543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。

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 identify 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 patient is a compound heterozygote of[ ＋ 40 to ＋ 43（-AAAC） -CD41/42 （-TCTT） ]/IVS-2-654（C to T） leading to 13-thalasscmia major. Con- dusion The triple mutation of [ ＋ 40 to ＋ 43（-A AAC）·CD41/42（-TCTF）/N] is a new genotype of beta-thalasscmia in Chinese.