Genotype-phenotype correlation of HbH disease in northern Iraq
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RESEARCH ARTICLE
Open Access
Genotype-phenotype correlation of HbH disease in northern Iraq Rawand P. Shamoon1,2* , Ahmed K. Yassin3,4, Ranan K. Polus1 and Mohamad D. Ali4
Abstract Background: HbH disease results from dysfunction of three, less commonly two, α-globin genes through various combinations of deletion and non-deletion mutations. Characterization of the mutations and the underlying genotypes is fundamental for proper screening and prevention of thalassaemia in any region. The aim of this study was to explore the genetic arrangements of HbH disease and to correlate the genotypes with the clinical phenotypes. Methods: A total of 44 HbH disease patients were enrolled in this study. They were clinically and haematologically assessed. The patients were tested for 21 common α-globin gene mutations using multiplex PCR and reverse hybridization. According to the genotype, the patients were categorized into two separate sub-groups, deletion and non-deletion types HbH disease. Results: Within the studied HbH disease patients, eight different α-globin gene mutations were detected in nine different genetic arrangements. The --MED and -α3.7 deletions were the two most frequently encountered mutations (37.5 and 35.2% respectively). Patients with deletion genotypes constituted 70.4%. The most common detected genotype was --MED/−α3.7 (59.1%), followed by αpoly-A1α/αpoly-A1α (13.6%). For the first time, coinheritance of two relatively mild mutations (−α3.7/ααAdana) was unpredictably detected in a 1.5 year-old child with Hb of 7.1 g/dL. Conclusion: The HbH disease patients’ clinical characteristics were variable with no ample difference between the deletion and non-deletion types. These results can be of benefit for the screening and management of thalassaemia in this region. Keywords: HbH disease, Genotype-phenotype correlation, Alpha-thalassaemia, Erbil, Iraq
Background α-thalassaemia is said to be the most common monogenic disorder worldwide. The genetic defects in the αglobin genes, which are mostly gene deletions, result in the absence or reduced production of α-globin chain in the hemoglobin tetramer [1]. Numerous mutations, deletion and non-deletion types, have been so far identified in the α-globin genes; some causes dysfunction of one αglobin gene, denoted as α+ mutations; others resulting in * Correspondence: [email protected] 1 Department of Pathology, College of Medicine, Hawler Medical University, Erbil, Iraq 2 Lab. Section, Thalassemia Care Center, Erbil, Iraq Full list of author information is available at the end of the article
deletion or deactivation of two α-globin genes, denoted as α0 alleles [2]. The clinical manifestations of these genetic defects vary. In heterozygous state, these mutations are usually of little clinical significance. However, the coinheritance of these mutations may result in a variety of clinical and haematological phenotypes. The most severe phenotype is hydrops fetalis, where all four α-globin genes are missing (−−/−−). Hemoglobin H (HbH) disease is a moderate clin
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