Alpha-Globin Gene Triplication in Central Thailand: Prevalence, Haematological Findings and Clinical Impact With Co-Inherited Beta-Globin Mutations.

OBJECTIVES

We aimed to ascertain the prevalence of ααα and ααα triplications in central Thailand and to characterise the phenotypes of individuals harbouring these variants.

MATERIALS AND METHODS

We performed a retrospective review of adult (≥ 18 years) samples submitted for polymerase chain reaction-based α-globin mutation analysis at Siriraj Hospital, Mahidol University, Bangkok (January 2012-December 2021). Haematological indices were compared between carriers and non-carriers of α-globin triplications, and clinical severity was assessed in those with co-inherited β-globin mutations.

RESULTS

Among 1559 subjects, α-globin triplication prevalence was 1.28%, with ααα (0.83%) more frequent than ααα (0.45%). Double heterozygosity for an α triplication and a β-globin mutation occurred in 0.9%. Individuals carrying ααα or ααα had lower mean haemoglobin levels (10.00 and 11.23 ± 1.85 g/dL, respectively) than those without triplication (12.35 ± 2.59 g/dL). Among heterozygous β-thalassaemia individuals, co-inheritance of ααα or ααα was associated with significantly reduced mean haemoglobin (8.38 ± 1.58 and 8.28 ± 1.15 g/dL, respectively). This contrasts with the non-triplication group (11.14 ± 1.86 g/dL). Of 14 subjects with double heterozygosity, 8 had thalassaemia intermedia and 6 had thalassaemia trait.

CONCLUSIONS

Although uncommon in central Thailand, α-globin triplications can exacerbate anaemia in individuals with co-inherited heterozygous β-globin mutations, supporting routine screening in symptomatic cases. : The authors have confirmed clinical trial registration is not needed for this submission.