The Frequency and Importance of Common α-globin Gene Deletions Among β-Thalassemia Carriers in an Iranian Population

BACKGROUND: β-thalassemia is the most common monogenic disorder in Iran, and one of the challenges in the screening of the carriers is the coinheritance of α-thalassemia mutations. In the view of high prevalence of α-thalassemia mutations in many parts of the country, the aim of this study was to determine the carrier frequency of common alpha deletions, as a secondary modifier in clinical manifestations of beta thalassemia, in known beta-thalassemia carriers and some hematology parameter changes. METHODS: The study included families referred from different primary health care centers with microcytic hypochromic anemia [MCV<80fl; MCH<27 pg] and A2>3.4%]. Genomic DNA was extracted from peripheral blood leukocytes by salting out method. For common β-globin gene mutation analysis, amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) and for rare β-thal alleles, DNA sequencing were used. Also, for investigation of common α-globin gene cluster deletions (−α3.7, −α4.2, --MED and −α20.5), multiplex Gap-PCR was performed. RESULTS: Among 227 β-thalassemia minor individuals studied, α-globin gene deletions were found in 43 cases: 37 heterozygote −α3.7 (16.3%), 5 homo −α3.7 (2.2%) and 1 --MED (0.44%). Also, the co-inheritance of α-globin gene deletion and triplication was not found in the studied individuals. CONCLUSION: Although it is highly recommended that physicians and genetic counselors involved in the screening program of beta-thal major in the country consider this phenomenon because of high prevalence of this coinheritance, hematologic indices changes are very slight.