title: Beta-thalassemia intermedia from southern Iran: IVS-II-1 (G-->A) is the prevalent thalassemia intermedia allele.
abstract: The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of beta-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of beta-thalassemia intermedia in Southern Iran; (ii) to verify the role of the -158 (G)gamma (C-->T) (Xmn I) polymorphism as a modulating factor in thalassemia intermedia; (iii) to test the validity of the multiplex and single mutation specific amplification refractory mutation system in analyzing the molecular defects causing beta-thalassemia in multiethnic populations; and (iv) to develop suitable strategies for the application of prevention protocols in Iran. To accomplish the task we have selected 87 beta-thalassemia intermedia patients and adapted the DNA methodology to detect the following 11 frequent mutations in Iran: codon 5 (-CT); frameshift codons (FSC) 8/9 (+G); codon 30 (G-->C); IVS-I-1 (G-->A); IVS-I-5 (G-->C); IVS-I-6 (T-->C); IVS-I-110 (G-->A); codons 36/37 (-T); codon 44 (-C); IVS-II-1 (G-->A); IVS-II-745 (C-->G). Because of the multiethnicity of the population we have also included the Indian IVS-I (25 bp deletion) and the Mediterranean IVS-I-130 (G-->C) and codon 39 (C-->T) mutations. Forty-eight patients were randomly studied for the Xmn I polymorphism together with 50 healthy volunteers as a control group. The molecular analysis conducted in Iran, identified only 31% of the alleles that were presumed to be thalassemic, revealing either a strategic or a technical insufficiency of the chosen method. However, the mutations with the highest prevalence in the country (IVS-II-1, IVS-I-110, IVS-I-1 and FSC 8/9) were found. As expected the IVS-II-1 defect, being the most frequent in south Iran, was present at the highest rate (24%). The Xmn I polymorphism was found in association with this prevalent mutation and was detected in the homozygous state in 87.5% of the patients homozygous for the IVS-II-1 (G-->A) mutation. The overall positivity for Xmn I was found in 40.6% of the thalassemic alleles vs. 14% in the non-thalassemic, confirming the hypothesis of an older event, antecedent to the IVS-II-1 mutation. In trying to assess a more suitable molecular detection method we intend to continue this study in collaboration with the European centers involved, applying more effective technologies and better defining the molecular spectrum of beta-thalassemia in the sub-populations. We also intend to verify the effect of alpha-thalassemia in the genotype/phenotype correlation of beta-thalassemia intermedia.
authors.affiliation: Department of Pediatrics, Nemazee Hospital, Shiraz, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Karimi
authors.forename: Hooman
authors.initials: H
authors.lastname: Yarmohammadi
authors.forename: Shirin
authors.initials: S
authors.lastname: Farjadian
authors.forename: Sirus
authors.initials: S
authors.lastname: Zeinali
authors.forename: Zahra
authors.initials: Z
authors.lastname: Moghaddam
authors.forename: Maria D
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards; D005838:Genotype; D007492:Iran / Q000453:epidemiology; D015810:Linkage Disequilibrium; D009154:Mutation; D010641:Phenotype; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control