Objectives: There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia.
Methods: A comprehensive hematology and DNA analysis was applied in the index patient and her mother.
Results: Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β0-thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named 'Hb Yala' according to the origin of this index family.
Discussion: This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or β0-thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found.
Conclusion: This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.
Keywords: Hb E/β-thalassemia; frameshift mutation; hemoglobin Yala; hemoglobin variant; non-transfusion-dependent thalasssemia; thalassemia; transfusion-dependent thalassemia; β-Globin mutation.