Distribution of β-Thalassemia Mutations in the Northern Provinces of Iran (original) (raw)
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International journal of hematology-oncology and stem cell research, 2015
Thalassemia syndromes are the most prevalent single gene disorders in Iran. This study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or Xmn1 SNP on disease phenotype in a large cohort of Iranian patients. In total, 433 patients were clinically classified into β-thalassemia major (TM) or intermedia (TI). Multiplex PCR, ARMS-PCR, RFLP-PCR and DNA sequencing were performed to identify both α- and β-globin gene mutations and Xmn1 polymorphism as well. All data were compared and analyzed by SPSS software in TM and TI groups, consequently. A total of 39 different β-globin mutations were identified. Among them, the most common were IVS IInt1 (40.33%) followed by IVS Int5 (9.56%), C30 (7.22%) and Fr8-9(7%). All patients were subjected to evaluate common α-globin gene deletions. The patients inherited concomitant mutations of α- and β-globin, showed no clinical modifications compared with those who had only β-...
Journal of biomedical science, 2017
Beta-thalassemia is common in the Mediterranean area as well as the Middle East and India. Official report in Iran revealed the average prevalence rate of carriers about 4%. More than 20 restriction fragment length polymorphisms (RFLPs) are known in the beta-globin gene cluster and used in the prenatal diagnosis (PND) services. Some of these locations may have low allele frequency and are not informative in the prenatal diagnosis. The current study aims to find new haplotypes and polymorphisms with high allele frequency in the local population. Two thousand three hundred fifty samples (1,321 male and 1,029 female) from the northern Iran, whom suspected to be the carriers either for alpha or beta thalassemia and referred to the local diagnostic laboratory as a routine services were investigated during five years, (2010-2015). The beta-globin gene was sequenced for all samples. Heterozygosity for five SNPs in the beta-globin gene was calculated separately. 383 individuals (16.29%) sho...
Spectrum of β-thalassemia Mutations in Iran, an Update
β-thalassemia major (β –TM) is the most common thalassemia severe phenotype among Iranians. In recent years, molecular understanding of pathogenesis of β –TM has provided a great opportunity regarding diagnostic issues. Creating comprehensive molecular databases provides highly sensitive diagnostic tools for β –TM and effective prenatal diagnosis (PND) molecular screening tests. Despite a large body of research on molecular basis of β –TM, there are few review papers that consider a general view on the distribution of β –TM mutations in Iran. In the current review, common genetic defects identified in Iranian β –TM patients since 2005 to 2014 have been described. In addition, the prevalences and distributional trends of recognized mutations were discussed. It was found that IVSII-1 (G>A) and IVSI-5 (G>C) were by far the most frequent mutations detected in Iranian patients. Other common reported mutations included FSC 8/9 (+G), IVS I-110 (G>A), FSC 36/37 (– T), IVSI-1 (G>A), IVSI (-25bp), and codon 44 (-C). In conclusion, it was found that molecular profile of β –TM is highly variable among different Iranian populations; in particular, it seems that ethnicity and intra-migration can be most important participating factors in controlling distributional patterns.
Hemoglobin, 2017
a-Thalassemia (a-thal) is the most common monogenic disease that is caused by the absence or reduced expression of a-globin genes. The aim of this study was to investigate common a-globin mutations and their associated haplotypes in four northern provinces of Iran (Gilan, Mazandaran, Golestan, Khorasan). One thousand, one hundred and ninety-one persons were tested for a-thal mutations by gap-polymerase chain reaction (PCR), reverse dot-blot hybridization, restriction fragment length polymorphism (RFLP) analysis and sequencing. Of the nine different mutations found, the most frequent were-a 3.7 (rightward deletion) (45.6%), polyadenylation site (a plyA2 a) (a2) (AATAAA>AATGAA; HBA2: c. Ã 92 A>G) (15.27%),-MED (Mediterranean deletion) (6.86%),-a 4.2 (leftward deletion), (6.17%), a CS a [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%),-a À5 nt (HBA2: c.95þ2_95þ6delTGAGG) (3.70%). All chromosomes bearing an a-globin point mutation [a plyA2 a,-a À5 nt a, a CS a, a plyA1 a (AATAAA> AATAAG; HBA2: c. Ã 94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the-a 3.7 deletion was associated with three distinct haplotypes. Our results indicate that a-thal mutations are heterogeneous and-a 3.7 and a plyA2 a are the most prevalent mutations in this region. The presence of-a 3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of a plyA2 a in Mazandaran Province, Iran compared to other parts of the country and the world, suggests a founder effect. Altogether, we here provide further data confirming the heterogeneity of the northern population of Iran. These data may contribute to the establishment of a national mutation database, more accurate genetic counseling and prenatal diagnosis (PND).
Frontiers in Pediatrics
BackgroundAlpha thalassemia is one of the most common hereditary hemoglobin disorders worldwide, particularly in the Middle East, including Iran. Therefore, determining the spectrum and distribution of alpha thalassemia mutation is a fundamental component of preventive approaches and management strategies.MethodsThe present study reviews the genetic testing and blood laboratory results of 455 candidates eligible for marriage who were suspected of being thalassemia carriers and on whom genetic testing was performed from 21 March 2013 to 31 December 2020 in Rasht City.ResultsA total of 114 (25.05%) alpha thalassemia cases were identified. Fifteen different alpha mutations were found. The most common mutation among the study population was −α3.7 deletion in 55 patients (48.24%), followed by Hb Constant Spring (C.S) in 21 patients (18.42%) and poly A2 in 16 (14.03%). Also, most of the patients were silent carriers. The deletion type of mutation was much more common than non-deletion mut...
Iranian Journal of Medical Sciences, 2009
Background: Beta thalassemia is a common inherited disease, resulting from one or more of 200 different mutations in the betaglobin gene. Qazvin province has attracted migrations of several different populations due to industrialization during the past five decades. The aim of this study was to define the molecular spectrum of beta-thalassemia mutations in Qazvin province. Methods: Ethylen diamin acetic acid-containing venous blood samples were collected from 100 patients with transfusiondependent beta-thalassemia from the department of Pediatrics in Qods hospital. Age, sex, history, and consanguinity between the parents were recorded by reviewing the patients' files. DNA was isolated from leukocytes using the standard procedure. Amplification refractory mutation system (ARMS) technique was used for molecular detection of mutations. Direct sequencing analysis was applied for DNA samples when no mutation was detected with ARMS. Results: Of the 200 chromosomes investigated, 11 types of mutations were identified by ARMS technique while direct sequencing revealed the remaining alleles (9 types of mutations). Total 20 different mutations discovered by this two-step approach. Abundant alleles (IVS II-1, IVS I-10, FSC 8/9) accounted for 59.3% of the mutations. IVS II-1 with a frequency of 31.3 % was the most common while HbS, Cd 74/75 and Cd 15, each with a frequency of 0.55%, had the least frequencies. Conclusion: Beta thalassemia mutations are very heterogeneous in Qazvin province. Extensive ethnic and genetic admixture has resulted in unexpectedly high number of different mutations, most of them similar to that of north and northwestern provinces of Iran. Different mutations in this region suggest migration of chromosomes from distant places and genetic admixture.
β globin mutations in Turkish, Northern Iraqi and Albanian patients with β thalassemia major
Thalassemia Reports
The mutation detection of β thalassemia is absolutely necessary for molecular diagnosis, as well as any genetic epidemiological study. The β globin gene has 3 exons and 2 introns, involved in β-thalassemic pathogenesis. The study aim of the study is to characterize the spectrum of β globin gene mutations in 136 Turkish, Northern Iraqi and Albanian pediatric β thalassemia major patients. After genomic DNA extraction from venous blood and amplification of the target DNA regions with PCR, genotyping was achieved by Sanger based DNA sequencing. The IVSI-110 G>A mutation was the most frequent allele in the Turkish and Albanian patients. In Northern Iraqi patients IVSI-1 G>A was is the most frequent. There are two mutations are firstly reported for Albania [c.*111 A>G 3’ UTR (rs63751128) and c.113 G>A (p.Trp38Ter, p.W38*) (rs35887507)] with this study. These findings may be of value for genetic counseling, premarital diagnosis, prenatal diagnosis and prevention programs.
Prenatal diagnosis (PND) of β-thalassemia in the Khuzestan province, Iran
2007
ABSTRACT β-Thalassemia is present in practically every caste group in Iran. Khuzestan is located in the southern part of the geographical region of Iran. The βthalassemia incidence in the Khuzestan province is between 2.6-3.7%, as reported by different researchers. Reverse dot blot hybridization and Amplification Refractory mutation Analysis (ARMS), were used to scan the entire β-globin gene to localize the mutation, followed by DNA sequencing for characterization.
Spectrum of α-thalassemia mutations in Qazvin Province, Iran
AFRICAN JOURNAL OF BIOTECHNOLOGY, 2011
α-Thalassemia is a widespread inherited disease particularly prevalent in the middle East Asia population, including Iran. The aim of this study was to define the molecular spectrum and frequency of α-thalassemia mutations in prospective couples of Qazvin province. A total of 120,000 subjects were studied during 10 years (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008). Individuals present with hypochromic and microcytic parameters with normal haemoglobin α-2 (HbA2), without iron deficiency were included in the study. Molecular detection of α-globin mutations were performed by gap-PCR, reverse dot blot hybridization (RDB) and sequencing. Results show that six different kinds of mutations are present in this region. In 22 subjects, most prevalent α-thalassemia mutations were α -3.7 , followed by α -20.5 and α 5nt . Most α-thalassemia couples had consanguineous relationships and Kordish ethnicity. In conclusion, in spite of relatively low incidence of α-thalassemia mutations in Qazvin province, the spectrum and frequency of mutations are different from other parts of Iran. It might be due to migration of several ethnic groups to Qazvin.