Haplotype Analysis in Carriers of ß-Globin Gene Mutation Facilitates Genetic Counseling in ß-Thalassemia: A Cross-Sectional Study in Kerman Province, Iran.

ABSTRACT

BACKGROUND: ß-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. ß-thalassemias are caused by mutations in the ß-globin gene, inherited in an autosomal recessive manner. Determining molecular defects in couples carrying ß-thalassemia is a prerequisite for prenatal diagnosis of the disease. In this regards, database of ß-globin gene haplotypes facilitates mutation detection of the gene and helps genetic counselors to reach the goals of ß-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 ß-thalassemia 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 ß-globin gene cluster, respectively. RESULTS: We identified 20 different types of ß-globin gene mutation in 449 ß-thalassemia carriers. Analysis of the pattern of Hind III/Gγ, Hinf I/5'ß, Hinc II/3'Ψß, Rsa I/5'ß, AvaII/ß 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 ß-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 ß-thalassemia carriers more straightforward and the process of mutation screening faster and more accurate.