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

Abstract

BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionsChinese 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 β0/βN and 1 β+/βN) with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β0/β0), the existence of other causative genetic determinants is remaining to be molecularly defined.

Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants

“…The incidence of this disease is high in tropical and subtropical areas, including southern China. In the southern Chinese regions of Guangdong and Guangxi, 2.54% and 6.78% of individuals are carriers for β-thalassemia, respectively [23]. The diagnosis of a β-thalassemia is usually based on the accurate measurement of HbA2 by using long separation programs on IE-HPLC or CE instruments [24].…”

β-Thalassemia Intermedia in Northern Iraq: A Single Center Experience

“…In one of these heterozygous patients there was a concomitant ααα / αα genotype, which would explain the TI phenotype in these patients and such alpha triplication increases the α  :  β imbalance among β -thal heterozygotes and has been implicated in TI in several earlier studies from Asia and the Mediterranean region [13, 15, 16, 19–21]. The other two heterozygous cases were associated with a normal alpha genotype, and thus their TI remains unexplained and we postulate that further unidentified genetic and/or environmental factors may be implicated.…”

Hemoglobinopathy: Molecular Epidemiological Characteristics and Health Effects on Hakka People in the Meizhou Region, Southern China

“…Gap-PCR was used to identify three deletion genotypes of HPFH/δβ-thalassemia including Chinese ( A γδβ) 0 thalassemia, Southeast Asian (Vietnamese) deletion and Thai ( A γδβ) 0 thalassemia (HPFH-6), which was the commonest genotypes in China [13], [14]. The primers and reaction system were performed as previous reports [14]–[15].…”