Screening for rare and novel β-globin gene mutations by high resolution melting analysis

Abstract

Rare and novel β-globin gene mutations could be misdiagnose in patients with α- and β-thalassemia in routine Hb typing and DNA analysis. In coinheritance of α- and β-thalassemia, Hb A₂ might be lower than normal level and thus arouses no suspicion for presence of β-thalassemia. Although the common β-globin gene mutations in a given region are detected in routine DNA tests, cases of co-inherited α-thalassemia can be missed in β-thalassemia detection if there is no prior indication. High resolution melting (HRM) analysis was used to scan β-globin genes in 140 samples. Rare and novel β-globin gene mutations were identified in three cases of β-thalassemia trait, namely, HBB: c.2T>G, Hb Monroe [HBB:c.92G>C] together with nt-42 [HBB: c.-92C>G] mutation and 14-nucleotide (+AGGGCAATAATTTC) insertion downstream of IVSII-561 together with IVSI-1 [HBB:c.92+1G>T] mutation. In addition, Hb Agenogi [HBB:c.271G>A] was present in one case of α-thalassemia trait, and among three cases of Hb H disease one co-inherited Hb Korle-bu [HBB:c.220G>A] and two nt-28 [HBB:c.-78A>G] mutation. Thus, HRM scanning for β-globin gene mutations provides a useful tool in providing information for counseling risk couples.