Molecular diagnosis of common alpha plus Thalassaemia deletions(3.7 kb, 4.2 kb) and alpha triplication in Sri Lanka

Abstract

The thalassaemias are a group of inherited blood disorders of haemoglobin synthesis which result from a deficiency of either alpha or beeta chains of haemoglobin. The a thalassaemia occurs mostly due to deletions or less frequently due to point mutations. One such type of alpha deletion referred to as alpha+ thalassaemia, occurs due to mostly 3.7 kb or 4.2 kb deletions. There is no consensus regarding the haemotological characteristics in individuals with a+ heterozygous condition It is important to resolve this issue as it likely that individuals with low red cell indices if du/to a thalassaemia trait would be subjected to unnecessary iron therapy. Unlike the case of p thalassaemia, prevalence studies of a thalassaemia in Sri Lanka are very limited. A total of 7539 subjects from all 25 districts in Sri Lanka were recruited. 2038 were found to have hypochromic microcytosis (Group 01). From the remainder with normal indices, 1305 were selected, as a control group (Group 02). Totaling 3343 subjects were genotyped for common alpha+ 3.7 kb and 4 2 kb deletions by using Gap PCR. The overall prevalence of a thalassaemia was found to be 9 51 % in Sri Lanka. The inter-regional variability of a thalassaemia prevalence was remarkable. 626 individuals were found to have various combination of the a+ deletions. Of them 95% cases had hypochromic microcytosis Only 5% had non hypochromic microcytosis. Those with a thalassaemia were further assessed for their red cell parameters, beeta thalassaemia and iron studies. Gender and ethnicity too were assessed. Just as much as a thalassaemia can cause hematological abnormalities, it might be expected that if excess a genes are co-inherited with ~ thalassaemia trait, it would cause alteration of the phenotype beeta thalassaemia trait. Hundred individuals were genotyped for common 3.7 kb triplicated a (Group 03). 44% had positives for a triplications. Of whom 36 had triple alpha antis 3.7 inherited with beeta heterozygous, developed p thalassaemia intermedia.Those with a triplication alone did not significantly affect to red cell morphology. We conclude that prevalence of a thalassaemia is higher than beeta thalassaemia in Sri Lanka. Single gene deletions can cause mild hypochromic microcytosis without anaemia, but double gene deletions can cause severe hypochromic microcytosis with mild anaemia. Excess a gene is an important cause of the thalassaemia intermedia in_ Sri Lanka. As part of the study we were able to successfully establish molecular diagnosis methods for common alpha deletions and alpha triplication (triple alpha.anti3 7).