Spectrum of beta-thalassemia in Jordan: Identification of two novel mutations

Two hundred and forty-four beta -thalassemia alleles were Identified from 1 35 unrelated occasionally and periodically transfusion dependent beta- and S/beta -thalassemia patients from all regions of Jordan. Allele identificat ion was achieved by PCR amplification of beta -globin genes, dot-blotting t he amplified DNA, hybridization with allele specific synthetic probes, and direct sequencing of amplified genomic DNA. A total of 19 different mutatio ns were detected, eight of them constituted about 86% of the Jordanian thal assemic chromosomes. These mutations were IVS1-110 (G>A) (25%), IVS2-1 (G>A ) (115%), IVS2-745 (C>G) (14.2%), IVS1-1 (G>A) (10%), IVS1-6 (T>C) (8.3%), codon 37 (G>A) (6.3%), codon 39 (C>T) (4.6%), and codon 5 (-C) (3.8%). The remaining eleven mutations were rare, presented with frequencies ranging be tween 0.4% and 1.6%. These included two novel mutations and four others det ected in Jordan for the first time. The novel mutations were the frame shif t (-C) at codon 49 and the substitution (A>C) at position -29 in the TATA b ox. Four alleles (1.6%) remained unidentified; having no abnormalities In t heir beta -globin gene sequences and therefore, constituted additional defe cts causing beta -thalassemia in the Jordanian population. These unknown al leles are expected to be candidates for upstream or downstream mutations af fecting the expression of beta -globin gene. The results provided the essen tial foundation for planning a national preventive program for thalassemia in Jordan and will help Improving the medical services for the patients and their families by helping their clinicians and genetic counselors in evalu ating their variants and designing their treatment regimens. Am. J. Hematol . 68:16-22, 2001. (C) 2001 Wiley-Liss, Inc.