THE β⁺-IVS-I-6 (T → C) MUTATION ACCOUNTS FOR HALF OF THE THALASSEMIA CHROMOSOMES IN THE PALESTINIAN POPULATIONS OF THE MOUNTAIN REGIONS

Abstract

A study of the spectrum of β-thalassemia mutations in the southern part of the West Bank of the Palestinian Authority revealed the presence of 10 different β-globin mutations. The study included 41 patients and 54 carriers of β-thalassemia and sickle cell anemia. The spectrum of mutations observed was typically Mediterranean. However, their relative frequencies was unique. The predominant allele was IVS-I-6 (T → C), with an exceptionally high frequency of 48.5% for this mutation. The homozygous IVS-I-6 patients had widely variable clinical presentations, from typical transfusion-dependent thalassemia major to non-transfusion-dependent thalassemia intermedia phenotype. Since it is so widespread in these West Bank populations, the IVS-I-6 mutation may date back to ancient times. The nonsense mutation at codon 37 (G → A) was found at a relatively high frequency of 11.3%, supporting the hypothesis that it originated in this region. The other mutations, at decreasing frequencies ranging from 9.5–1.5%, were: IVS-I-110 (G → A), frameshift codon 5 (−CT), IVS-I-1 (G → A), IVS-II-1 (G → A), Hb S [β6(A3)Glu → Val], frameshift codons 8/9 (+G), codon 39 (C → T), and −30 (T → A). Our findings will improve health care for the Palestinian population, and also has implications for the study of the origin and spread of thalassemia in the Middle East.