Genotype-phenotype correlation of HbH disease in northern Iraq

Abstract

Background HbH disease results from dysfunction of three, less commonly two, alpha-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 alpha-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 alpha-globin gene mutations were detected in nine different genetic arrangements. The --(MED)and -alpha(3.7)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)/-alpha(3.7)(59.1%), followed by alpha(poly-A1)alpha/alpha(poly-A1)alpha (13.6%). For the first time, coinheritance of two relatively mild mutations (-alpha(3.7)/alpha alpha(Adana)) 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.