64例地中海贫血常见与罕见基因型的表型分析

Phenotypic analysis of common and rare genotypes in 64 cases of thalassemia

目的对常见、罕见地贫基因型患者的表型分析,探讨不同基因型与表型间差异。方法采用反向斑点杂交及gap-PCR技术检测来自南宁、柳州、百色等3地区64例患者地贫基因型并进行分组。收集患者治疗史、血液学与铁代谢的生化指标。采用Kruskal-Wallis检验或Welch one-way ANOVA检验分析患者表型特征。结果检出58例常见基因型:30例β~0/β~0,28例HbH CS(α^(CS)α/--^(SEA));6例罕见基因型:3例Hb CS纯合突变,3例HbH(-α^(3.7)/--^(SEA))复合β~0/β~0。表型分析显示,β~0/β~0患者无输血生存时间最短,临床症状最重,HbH CS患者最轻,但临床表型异质性很大。Hb CS纯合突变与HbH CS患者相比,输血依赖程度与铁负荷明显重于后者。HbH复合β~0/β~0患者临床表型与β~0/β~0患者相比差异无统计学意义,但表型严重性呈下降趋势。Hb CS纯合突变、HbH复合β~0/β~0患者表型与β~0/β~0患者相似,极易误诊,需分子诊断以明确基因型。结论地贫基因型与表型存在多样性与复杂性特点,β-地贫表型重于α-地贫,α-地贫表型异质性大于β-地贫,罕见地贫表型类似β-地贫,Hb CS纯合突变表型重于HbH CS。

Objective Phenotypic analysis of patients with common and rare thalassemia genotypes was conducted to explore the differences between different genotypes and phenotypes.Methods The 64 patients with thalassemia from Nanning,Liuzhou and Baise were detected by reverse dot blot and gap-PCR to identify the genotypes and grouped according to the results.Treatment history,hematology and iron metabolism biochemical indexes were collected.Kruskal-Wallis test or Welch one-way ANOVA test were used to analyze phenotypic characteristics of patients.Results 58 common genotypes were detected,including 30β~0/β~0 patients,28 HbH CS patients(α~(CS)α/--~(SEA))and 6 patients with rare genotypes,which is included 3 homozygous mutation of Hb CS patients and 3 HbH(-α~(3.7)/--~(SEA))co-inheritedβ~0/β~0 patients.Phenotypic analysis showed thatβ~0/β~0 patients had the shortest transfusion-free survival time and the most severe clinical symptoms,while HbH CS patients had the mildest symptoms,but with a wide range of clinical phenotypic heterogeneity.Hb CS homozygous patients are significantly more transfusion-dependence and more iron burden compared to HbH CS patients.It is no significant difference in the phenotype of HbH co-inheritedβ~0/β~0 compared withβ~0/β~0 patients,but the phenotype severity showed a downward trend.The phenotype of both homozygous mutation of Hb CS and HbH co-inheritedβ~0/β~0 are similar to that ofβ~0/β~0 patients,which is easy to misdiagnose,and molecular diagnosis is needed to identify the genotype of patients.Conclusion The genotypes and phenotypes of thalassemia demonstrate great complexity and diversity.β-thalassemia patients have a more severe phenotype thanα-thalassemia patients.Phenotypic heterogeneity is greater in patients withα-thalassemia than in those withβ-thalassemia.The phenotype of the rare genotype is similar to that ofβ-thalassemia,in which the phenotype of homozygous mutation of Hb CS is more severe than that of HbH CS.