Molecular spectrum of Hb H disease and characterization of rare deletional α-thalassemia found in Thailand

Abstract

Hb H diseases with the clinical features of thalassemia are found in many parts of the world, including Southeast Asia and southern China. There are limitations in molecular data from the population of Thailand, which includes multiple ethnic groups. Here, we characterized the molecular basis of the disease among a large cohort from this region. A total of 479 unrelated Thai patients with Hb H disease were studied. Mutations of the α-globin gene were characterized by conventional gap-PCR and rare genotypes were identified by MLPA analysis and direct DNA sequencing. The molecular characterization showed five common Hb H genotypes (472/479; 98.54%), including three deletional types (–^SEA/-α^3.7; n = 312), (–^SEA/-α^4.2; n = 26), (–^THAI/-α^3.7; n = 1) and two non-deletional types (–^SEA/α^CSα; n = 131), (–^SEA/α^Pakséα; n = 2). Herein, we firstly report a rare genotype of Hb H disease with (–^SA/-α^3.7; n = 1) that has not been documented in Thailand, and rare genotypes related to (–^SEA/-α^16.6; n = 1), and (–^SEA/α^QSα; n = 3) as well. The remaining two cases could not be characterized. The hematological parameters demonstrated that the clinical phenotype of non-deletional Hb H diseases is more severe than the deletional type of α⁺-thalassemia. The molecular spectrum of α-thalassemia is useful for prevention and thalassemia control and genetic counseling for couples at risk in this region.

Keywords:

• Hemoglobin H disease
• MLPA analysis
• α-thalassemia
• rare genotype
• Thailand

Ethical approval

Ethical approval for the study was obtained from the Institutional Review Board of Srinakharinwirot University, Thailand (SWUEC-077/2562X).

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This research project was supported by a grant from Srinakharinwirot University, Thailand 2019 (government subsidies; Grant No. 007/2562).