Open Access Highly Accessed Research article

The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity

Wanqun Chen14, Xinhua Zhang2, Xuan Shang1, Ren Cai3, Liyan Li1, Tianhong Zhou2, Manna Sun1, Fu Xiong1 and Xiangmin Xu1*

  • * Corresponding author: Xiangmin Xu xixm@fimmu.com

  • † Equal contributors

Author Affiliations

1 Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China

2 Department of Hematology, 303 Hospital of People's Liberation Army of China, Nanning, Guangxi 530021, China

3 Department of Medical Genetics, Liuzhou Municipal Maternity and Child Healthcare Hospital, Liuzhou, Guangxi 545001, China

4 Department of Biochemistry, Medical College, Jinan University, Guangzhou, Guangdong 510632, China

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BMC Medical Genetics 2010, 11:31  doi:10.1186/1471-2350-11-31

Published: 25 February 2010

Abstract

Background

The clinical syndrome of thalassemia intermedia (TI) results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF) and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients.

Methods

We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations.

Results

A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20) in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited αααanti-3.7 triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β+-thalassemia mutation was the most common (49/97), hemoglobin E (HbE) variants was second (27/97), and deletional hereditary persistence of fetal hemoglobin (HPFH) or δβ-thalassemia was third (11/97). Two novel mutations, Term CD+32(A→C) and Cap+39(C→T), have been detected.

Conclusions

Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β0N and 1 β+N) with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β00), the existence of other causative genetic determinants is remaining to be molecularly defined.