β-thalassemia intermedia from Southern Iran: IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele
Mehran Karimi, Hooman Yarmohammadi, Shirin Farjadian, Sirus Zeinali, Zahra Moghaddam, Maria D. Cappellini, Piero C. Giordano
Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico
The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of β-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of β-thalassemia intermedia in Southern Iran; (ii) to verify the role of the - 158 Gγ (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 β-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 β-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 β-thalassemia in the sub-populations. We also intend to verify the effect of α-thalassemia in the genotype/phenotype correlation of β-thalassemia intermedia.
https://doi.org/10.1081/HEM-120005452
beta-Thalassemia
Karimi, M., Yarmohammadi, H., Farjadian, S., Zeinali, S., Moghaddam, Z., Cappellini, M. D., & Giordano, P. C. (2002). β-thalassemia intermedia from Southern Iran: IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele. Hemoglobin, 26(2), 147-154. https://doi.org/10.1081/HEM-120005452
β-thalassemia intermedia from Southern Iran : IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele. / Karimi, Mehran; Yarmohammadi, Hooman; Farjadian, Shirin; Zeinali, Sirus; Moghaddam, Zahra; Cappellini, Maria D.; Giordano, Piero C.
In: Hemoglobin, Vol. 26, No. 2, 2002, p. 147-154.
Karimi, M, Yarmohammadi, H, Farjadian, S, Zeinali, S, Moghaddam, Z, Cappellini, MD & Giordano, PC 2002, 'β-thalassemia intermedia from Southern Iran: IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele', Hemoglobin, vol. 26, no. 2, pp. 147-154. https://doi.org/10.1081/HEM-120005452
Karimi M, Yarmohammadi H, Farjadian S, Zeinali S, Moghaddam Z, Cappellini MD et al. β-thalassemia intermedia from Southern Iran: IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele. Hemoglobin. 2002;26(2):147-154. https://doi.org/10.1081/HEM-120005452
Karimi, Mehran ; Yarmohammadi, Hooman ; Farjadian, Shirin ; Zeinali, Sirus ; Moghaddam, Zahra ; Cappellini, Maria D. ; Giordano, Piero C. / β-thalassemia intermedia from Southern Iran : IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele. In: Hemoglobin. 2002 ; Vol. 26, No. 2. pp. 147-154.
@article{2cf7b6c15c9f4dab9b50171b52142627,
title = "β-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 β-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of β-thalassemia intermedia in Southern Iran; (ii) to verify the role of the - 158 Gγ (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 β-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 β-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 β-thalassemia in the sub-populations. We also intend to verify the effect of α-thalassemia in the genotype/phenotype correlation of β-thalassemia intermedia.",
author = "Mehran Karimi and Hooman Yarmohammadi and Shirin Farjadian and Sirus Zeinali and Zahra Moghaddam and Cappellini, {Maria D.} and Giordano, {Piero C.}",
doi = "10.1081/HEM-120005452",
journal = "Hemoglobin",
publisher = "Informa Healthcare",
T1 - β-thalassemia intermedia from Southern Iran
T2 - IVS-II-1 (G→A) is the prevalent thalassemia intermedia allele
AU - Karimi, Mehran
AU - Yarmohammadi, Hooman
AU - Farjadian, Shirin
AU - Zeinali, Sirus
AU - Moghaddam, Zahra
AU - Cappellini, Maria D.
AU - Giordano, Piero C.
N2 - The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of β-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of β-thalassemia intermedia in Southern Iran; (ii) to verify the role of the - 158 Gγ (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 β-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 β-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 β-thalassemia in the sub-populations. We also intend to verify the effect of α-thalassemia in the genotype/phenotype correlation of β-thalassemia intermedia.
AB - The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of β-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of β-thalassemia intermedia in Southern Iran; (ii) to verify the role of the - 158 Gγ (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 β-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 β-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 β-thalassemia in the sub-populations. We also intend to verify the effect of α-thalassemia in the genotype/phenotype correlation of β-thalassemia intermedia.
U2 - 10.1081/HEM-120005452
DO - 10.1081/HEM-120005452
JO - Hemoglobin
JF - Hemoglobin
10.1081/HEM-120005452