Identification of three novel mutations [-41 (A>C), codon 24 (-G), and IVS-I-109 (-T)], in a study of beta-thalassemia alleles in the Isfahan region of Iran.

Beta-thalassemia (beta-thal) is one of the most common autosomal recessive disorders in Iran, with more than 15,000 registered cases of thalassemia major in the country. Iran has a multiethnic society and knowledge of the mutation spectrum and regional distribution is an essential requirement for health planning and a prenatal diagnosis program. We have determined the spectrum of mutations in patients from the Isfahan region of Iran. A study of 190 chromosomes revealed 24 different mutations, including three novel ones: -41 (A>C), IVS-I-109 (-T) and codon 24 (-G). The most common mutation was IVS-II-1 (G>A) (20.5%), followed by IVS-I-5 (G>C) (11%). The findings for the Isfahan region confirm the extremely heterogeneous nature of the molecular basis of beta-thal in Iran. The results show that a strategy of using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for 14 of the most common mutations and DNA sequencing for the rare mutations can be used for prenatal diagnosis of beta-thal in this region.

Characterization of a novel deletion causing beta-thalassemia major in an Afghan family.

We have identified and characterized a novel beta-globin gene deletion mutation in a family of Afghan ancestry. The proband was a 10-year-old transfusion-dependent female with the phenotype of beta-thalassemia major (beta-TM). DNA sequencing of the beta-globin gene showed no abnormalities. Multiplex ligation-dependent probe amplification (MLPA) showed reduced/absent probe height of the probe covering the 5' end of the beta-globin gene indicating a possible deletion. Gap-polymerase chain reaction (gap-PCR) produced junctional fragments and direct sequencing of the product revealed that the 5' breakpoint was 478 nucleotides upstream of the Cap site and the 3' breakpoint was in the second exon of the beta-globin gene, giving a deletion size of 909 bp. The proband was homozygous and the parents were heterozygous for the deletion. This is the first report of a large beta-thalassemia (beta-thal) deletion mutation in this ethnic group.