A large cohort of Hb H disease in northeast Thailand: A molecular revisited, diverse genetic interactions and identification of a novel mutation

Abstract

Background and aimsTo update the molecular characteristics of α-thalassemia in northeast Thailand, the molecular basis and genetic interactions of Hb H disease were examined in a large cohort of patients. Materials and methodsA study was done on 1,170 subjects with Hb H disease and various genetic interactions encountered during 2009–2023. Hb and DNA analyses were carried out. ResultsAs many as 40 genotypes with several known, previously undescribed, and novel mutations were observed. These included 698 subjects (59.8 %) of Hb H disease, 357 (30.6 %) with EABart’s disease, 63 (5.4 %) with EEBart’s disease, 18 (1.7 %) with abnormal Hbs, 17 (1.5 %) with β-thalassemia, and 4 (0.4 %) with EFBart’s or EFABart’s disease. The molecular basis of 13 subjects (1.1 %) remains unknown. The α0-thalassemia included --SEA (n = 1,139, 97.4 %) and --THAI (n = 21, 1.8 %). Two rare mutations were identified in 3 subjects (0.3 %) with --SA and --CR deletions. For α+-thalassemia, −α3.7 kb del (n = 626, 53.5 %), Hb Constant Spring (n = 415, 35.5 %), −α4.2 kb del (n = 44, 3.8 %), Hb Paksé (n = 36, 3.1 %), and Hb Q-Thailand (n = 19, 1.6 %), were detected. Ten rarer α+-thalassemia were identified, including a novel mutation, namely the Hb Chumphae (HBA2:c.32T>A). The Hb H-Lansing-Ramathibodi, Hb H-Jax, and Hb H-Chumphae are hitherto undescribed in this region. PCR-based diagnostic methods for these α-thalassemia defects were described. ConclusionsThis study confirms the diverse heterogeneity and genetic interactions causing Hb H disease in northeast Thailand. The results should prove useful for laboratory diagnosis and genetic counseling of this genetic disorder in the region.