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/-α3.7; n = 312), (–SEA/-α4.2; n = 26), (–THAI/-α3.7; n = 1) and two non-deletional types (–SEA/αCSα; n = 131), (–SEA/αPakséα; n = 2). Herein, we firstly report a rare genotype of Hb H disease with (–SA/-α3.7; n = 1) that has not been documented in Thailand, and rare genotypes related to (–SEA/-α16.6; n = 1), and (–SEA/αQSα; 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. © 2020 Medisinsk Fysiologisk Forenings Forlag (MFFF).