α0-thalassemia in affected fetuses with hemoglobin E-β0-thalassemia disease in a high-risk population in Thailand

Objectives: A co-inheritance of alpha(0)-thalassemia can ameliorate the clinical severity of the hemoglobin (Hb) E-beta-thalassemia disease. This information should be provided at prenatal diagnosis. Identification of alpha(0)-thalassemia in an affected fetus is therefore valuable. We have explored this genetic interaction in a large cohort of affected fetuses with hemoglobin (Hb) E-beta(0)-thalassemia in northeast Thailand. Methods: A study was done retrospectively on 1,592 couples at risk of having fetuses with Hb E-beta(0)-thalassemia, encountered from January 2011 to December 2019. A total of 415 left-over DNA specimens of the affected fetuses with Hb E-beta(0)-thalassemia disease were further investigated. Examination of alpha(0)-thalassemia was done using gap-PCR or a multiplex PCR assay for simultaneous detection of Hb E and alpha(0)-thalassemia mutations. Results: Of the 415 affected fetuses, the two most common beta(0)-thalassemia genes found were the codons 41/42 (-TTCT) (199/415; 48.0%) and codon 17 (A T) (115/415; 27.7%). alpha(0)-thalassemia was found unexpectedly in 21 (5.1%) fetuses. Hematologic phenotypes of the parents indicated that it was impossible to differentiate a pure beta(0)-thalassemia carrier from a double beta(0) -thalassemia/alpha(0)-thalassemia heterozygote unless DNA analysis is performed. In contrast, a reduced level of Hb E in the Hb E carrier (<25%) is a valuable marker for predicting double heterozygosity for Hb E/alpha(0)-thalassemia. This could be further confirmed using a multiplex PCR assay. Conclusions: There is a high prevalence of co-inheritance of alpha(0)-thalassemia in fetuses with Hb E-beta(0)-thalassemia disease. In a high-risk population such as Thailand, we recommend screening for alpha(0)-thalassemia in all affected fetuses with Hb E-beta(0)-thalassemia disease and providing complete genetic information to the parents to make appropriate decisions at prenatal diagnosis and genetic counseling.