Phenotyping and genotyping studies in a family with the compound heterozygosity for a deletional δβ-thalassemia and a β-thalassemia

Objective To investigate the relationship between genotype and phenotype of a deletional δβ thalassemia and explore an approach to rapid prenatal diagnosis for compound heterozygotes of this defect and a β thalassemia.Methods A total of ten members in a Chinese family who had a 5 year old propositus with thalassemia major and requested prenatal diagnosis for the second pregnancy were investigated. For genotyping analysis, the deletional δβ thalassemia was characterized by gap PCR method and β thalassemia mutations were defined by reverse dot blot(RDB). For phenotyping analysis, hematological data including the RBC indices, quantification of HbF and HbA 2 by Hb electrophoresis and the ratio of globin chain Gγ/( Gγ + Aγ) analyzed by capillary electrophoresis (CE) were obtained.Results The propositus inherited her mother's δβ thalassemia gene mutation and her father's CD41 42( CTTT) frameshift mutation. Of nine members in this family screened for this type of deletion, four were positive and the phenotype could be explained satisfactorily by genotype. The results of prenatal diagnosis showed that the fetus was normal and had no β globin gene defects in both chromosomes. Conclusion This is the first time to have performed prenatal diagnosis in Chinese family at risk of compound heterozygotes for β thalassemia and δβ thalassemia in mailand China. The strategy to analyze the disease presented here may be a valuable reference to the similar problem.