Genotype–phenotype association in alpha-thalassemia cohort in a population with high prevalence of alpha and beta-thalassemia: importance of genetic screening

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Abstract

Purpose
Alpha and beta-thalassemias are common inherited hemoglobinopathies caused by reduced synthesis of alpha and beta-globin chains, respectively. Based on the type of mutation, the spectrum of hematological indices could be variable. This study aimed to determine the influence of coinheritance of alpha and beta-globin mutations on anemia severity.
Patients and methods
A total of 1415 patients with thalassemia, including alpha, beta, and alpha-beta thalassemia that were referred to the genetic center of premarital and prepregnancy screening were enrolled in this retrospective study. Hematological indices including complete blood count and hemoglobin A2 levels as well as genotypes of alpha and beta globin genes were considered. Gap-PCR, reverse dot–blot, restriction fragment length polymorphism, and sequencing were recruited for molecular analysis.
Results
The frequency of participants with alpha-globin deletion ( = 912) was ~ 2.5 times more than those with a point mutation ( = 392). The most common alpha-globin gene deletion and point mutation were HBA2:c. 94_95delAG (or HBA1) (del 3.7 kb) and AATAAA > AATGAA; HBA2: c.*92 A>G (PA2), respectively. Patients with beta-globin mutation had a lower hematological index in comparison with those with alpha-globin mutation. Moreover, alpha-globin mutation could moderate the phenotype of beta-thalassemia carriers.
Conclusion
Considering both alpha-globin and beta-globin gene mutations in the diagnosis of beta-thalassemia, especially in high-prevalence thalassemia regions showing genetic heterogeneity of the disease, may lead to a more accurate genetic counseling in the context of premarital and prepregnancy screening for thalassemia prevention.

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