First report of the spectrum of δ-globin gene mutations in Omani subjects - identification of novel mutations.

Abstract

Both coinheritance of thalassemic δ-globin mutation and coexistence of iron deficiency anemia (IDA) tend to decrease HbA2 (α2 δ2 ) level and thereby poses a diagnostic conundrum in β-thalassemia trait. We retrospectively studied 78 Omani subjects, presenting with low HbA2 level by high-performance liquid chromatography (HPLC), and their DNA was sequenced for the presence of mutations in the δ-globin gene (HBD). In these subjects, their serum ferritin levels allowed evaluation of the degree of iron deficiency. Overall, six different δ-globin gene mutations were observed in 40 study subjects (51.3%) and IDA in 33 subjects, with the remaining five subjects showing normal HBD sequence and serum ferritin level. Among the subjects with δ-globin gene mutations, seven had an associated IDA confirmed by significantly low serum ferritin levels. Heterozygosity for the delta (+) cd27G-->T mutation (HbA2 -Yialousa; HBD: c.82G>T) was the most common abnormality observed (n = 26, 66.6%) followed by heterozygosity for HBD c.-118C->T (d -68 C->T) (n = 6, 15.4%), for cd16G-->C (n = 4, 10.3%), for cd98G-->A (n = 2, 5.1%), for cd142G-->C (n = 1, 2.6%), and for cd147G-->T (n = 1, 2.6%). These delta mutations exhibit low HbA2 either due to a shift in the HPLC position or due to their bona fide thalassemic feature. Two mutations, namely cd142 G-->C (GCC to CCC, Ala to Pro) and stop codon cd147 G-->T (stop to Leu with elongation of 15 amino acids), herein first reported are novel. Coexistence of IDA could lead to erroneous diagnostic interpretation unless it is specifically looked for.