Hb Q-Thailand [α74(EF3)Asp→His]: Gene Organization, Molecular Structure, and DNA Diagnosis

Abstract

Hb Q-Thailand [alpha 74(EF3)Asp-->His] is often found in Thailand, China, and other Southeast Asian countries. The alpha-Q-Thailand gene is strongly linked to an alpha gene deletion and has important implications in the identification and diagnosis of hemoglobinopathies and thalassemias. The alpha-Q-Thailand mutation was previously mapped to the alpha 1 gene in a study of Chinese patients. In this paper, a Thai patient with Hb Q-Thailand/Hb H disease and his mother were studied at the DNA level, and the gene organization of Hb Q-Thailand in the Thai patient was found to be the same as that of Chinese patients (i.e. the Hb Q-Thailand gene is located on the alpha 1 gene of chromosome #16, while the -4.2 kb or leftward deletion involves the alpha 2 gene). Also, the GAC-->CAC mutation proposed at codon 74, has been confirmed by DNA sequencing and a simple and accurate method for diagnosis of the Hb Q-Thailand variant has been developed based on restriction enzyme analysis. Since the GAC-->CAC mutation generates new cutting sites for both restriction enzymes Apa LI and Hgi AI, polymerase chain reaction amplification of a specific region around codon 74, followed by digestion with these enzymes and agarose gel electrophoresis of the digested products, permits rapid and accurate identification of Hb Q-Thailand.

Association of Hb Q‐Thailand with homozygous Hb E and heterozygous Hb Constant Spring in pregnancy

“…With this PCR analysis, we identified the 4.2 kb deletional α ‐thalassemia 2 in P1, P1's father, P1's sister and P2 and the Hb CS gene in P2 and P2's father who was a carrier of Hb CS (Table 1). Further analysis by DNA sequencing of the amplified α 1 globin genes of the two probands identified the same G AC (Asp)– C AC (His) mutation at codon 74, corresponding to the Hb Q‐Thailand described previously (5, 8). Therefore with this analysis, we were able to conclude that P1 was a homozygous Hb E with Hb Q‐Thailand and P2 was a double heterozygote for Hb Q‐Thailand and Hb CS, both of which have not previously been encountered.…”

Hb QIndia and its interaction with β–thalassaemia: a study of 64 cases from India

“…Structural analysis shows that Hb Q results from the substitution of histidine for aspartic acid in one of the α-chains of Hb A. 2 Three types of Hb Q have been reported in the literature, based on the position of the amino acid replacement, and these are Hb Q India (α 1 64), 3 Hb Q Thailand (α74) 4 and Hb Q Iran (α75). 2 Several families of Hb Q interacting with α-thalassaemia have been reported among south-east Asians.…”

Hemoglobinopathies in Southeast Asia: Molecular Biology and Clinical Medicine

“…Hb H-Hb CS disease in association with Hb E also produces more severe clinical features (9-1 1). Other genotypes also lead to Hb H disease, such as Hb Q (Mahido\)-Hb H (--/-aQ) and Hb Suandok-Hb H (-/asDa) diseases (12,13). Hb H disease is characterized by Hb types of A+H and the demonstration of intra-erythrocytic Hb H inclusion bodies in the majority of red blood cells.…”