Haplotype Analysis in Carriers of β-globin Gene Mutation Facilitates Genetic Counseling in β-thalassemia: A Cross-Sectional Study in Kerman Province, Iran

Background: β-thalassemia is characterized by reduced synthesis of the hemoglobin beta chain that results in microcytic hypochromic anemia and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. β-thalassemias are caused by mutations in the β-globin gene, inherited in an autosomal recessive manner. Determining molecular defects in couples carrying β-thalassemia is a prerequisite for prenatal diagnosis of the disease. In this regards, database of β-globin gene haplotypes facilitates mutation detection of the gene and helps genetic counselors to reach the goals of β-thalassemia prevention program. Methods: In this cross-sectional study, 255 couples attended genetic counseling between December 2017 and January 2019 in Afzalipour Hospital, Kerman University of Medical Scinces, Kerman, Iran as suspicious of βthalassemia carriers. Furthermore, they were investigated using amplification refractory mutations system-polymerase chain reaction and restriction fragment length polymorphism methods for mutation screening and haplotype analysis of polymorphic sites in β-globin gene cluster, respectively. Results: We identified 20 different types of β-globin gene mutation in 449 β-thalassemia carriers. Analysis of the pattern of Hind III/Gγ, Hinf I/5′β, Hinc II/3′Ψβ, Rsa I/5′β, AvaII/β and Hind III/Aγ polymorphic sites in 257 alleles of informative families revealed 17 different haplotypes. Haplotype 1 (77.24%) showed strong linkage with the most common mutation IVSI-5 while haplotype 5 (66.67%) was associated with the second frequent mutation IVSII-1. Conclusion: To our knowledge, these β-globin haplotypes are reported for the first time which are different with those found in other parts of Iran. The current haplotypes pattern data makes the counseling of β-thalassemia carriers more straightforward and the process of mutation screening faster and more accurate.