COMBINATION OF IVS2.849 A-G WITH IVS1.1 G-A: A Mutation of β-Globin Gene in a Turkish β-Thalessemia Major Patient

Abstract

Beta-thalassemia, which is an autosomal recessive disease, is among the most common hemoglobinopathies in Antalya, Turkey. Mutations found in Turkish beta-thalassemia patients constitute a heterogeneous group, which is mostly composed of point mutations and, only in very rare cases, a deletion or an insertion causes affected or carrier phenotypes. Reverse dot blot hybridization (RDBH) method is used for screening common mutations, and sequence analysis and silver staining were performed consecutively to detect any uncommon mutation. The authors report a first Turkish family with a rare variant--intervening sequence 2 (IVS2) 849 (A-G). The proband's mother and father were determined as carriers of IVS2.849 (A-G) and IVS1.1 (G-A) mutations, respectively. Proband is the first child of the family and she has an IVS2.849 (A-G)/IVS1.1 (G-A) genotype with ss-thalassemia major phenotype. Prenatal diagnosis was performed for the second child, and genotype of the fetus was determined as IVS2.849 (A-G)/Normal. This first report of IVS2.849 (A-G) mutation in Turkish population shows that there are many more mutations contributing the heterogeneity of the mutation spectrum of beta-globin gene in the Turkish population, which indicates migrations of different ethnic origins.

Interaction of Hb South Florida (codon 1; GTG→ATG) and HbE, with β-thalassemia (IVS1-1; G→A): expression of different clinical phenotypes

“…The presence of IVS1-1(G→A) in this Malaysian Malay family may be a result of ancestral migration from countries bordering the Mediterranean Sea as the Malaysian Malays have ancestral links with Turkey, Persia, and the Middle East. This is further supported as IVS1-1(G→A) was also reported in β-thalassemia cases from the Aegean Region of Turkey [13,18]. However, it appears more likely that the IVS1-1(G→A) β-globin gene mutation may have resulted from migration of Indonesians to Malaysia or intermarriages of Malaysians with Indonesians as this mutation has been reported to be present in Indonesian β-thalassemia individuals with a frequency of 1.7% [15].…”