Prenatal diagnosis (PND) of β-thalassemia in the Khuzestan province, Iran (original) (raw)
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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...
Distribution of β-Thalassemia Mutations in the Northern Provinces of Iran
Hemoglobin, 2007
Background: β-thalassemia is a common autosomal recessive disorder resulting from over 200 different mutations of beta globin genes. The aim of the present study was to identify the distribution and frequency of the most common β-thalassemia mutations among the population of Isfahan Province in central Iran. Methods: The data presented here were derived from a total of 114 β-thalassemia chromosomes of 18 affected patients and 78 unrelated carriers identified in our screening program. Furthermore, 23 pregnant women were analyzed among couples with a PND request for β-thalassemia. Allele identification was carried out using routine Reverse Dot Blot, ARMS, and genomic sequencing.
Clinical and Experimental Medicine, 2004
β-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 β-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71–72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Gγ(Aγδβ)° and 45-kb Filipino deletions. The 192 β-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 β-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of β-thalassemia. β-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese β-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay β-thalassemia carrier. The β-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of β-thalassemia in Malaysia.
β-Thalassemia Caused by De novo Mutation in the β globin Gene Identified in Two Bangladeshi Families
Journal of Blood Disorders & Transfusion
De novo mutations represent a unique example of how rare mode of inheritance of genetic variations can influence the onset of genetic diseases. Most of the mutations causing β-thalassemia in Bangladeshi population were found to be inherited germ line. The study aimed to present two cases of De novo mutations of the β-globin gene causing β thalassemia. Out of one hundred Bangladeshi β-thalassemia carrier families who were advised for both pre and postnatal molecular characterization of the β-globin gene to detect the mutation, two cases of De novo mutations were identified in two Bangladeshi families, which is the first of this type of mutation inheritance in Bangladesh. Mutations were determined by sequencing of the entire β-globin gene by Sanger method. In one family as case A, the foetus proband in the amniotic fluid was found homozygous for the mutation in the codon 26 (G>A) (G>A) [HBB: c.79G>A] and was diagnosed as the β-thalassemia major. The paternal allele was normal and only the mother carried one mutant allele. In another family as case B, the proband in the blood of the affected child was found homozygous for the mutation IVS-I-5 (G>C) [HBB: c.92+G>C]. The father did not carry any mutation while the mother was heterozygous for the mutation. In both cases, the possibility of non-paternity was excluded by using STR-based parentages testing, indicating that the acquired mutation in the probands was the result of a De novo event. The study demonstrates the significance of the prenatal diagnosis of β-thalassemia by DNA sequencing to detect novel, rare or De novo mutation that cannot be identified during screening by haemoglobin electrophoresis.
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.
Mediterranean Journal of Hematology and Infectious Diseases
Background and objective: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit β (HBB) gene. In a study of β-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran we aimed to recognize the most common mutations in the region and to find a possible link between these mutations and some of the relevant hematological indices.Methods: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical HBB mutations among 1593 individuals, suspected of having a mutated HBB allele from March/2011 to January/2018. Sanger sequencing of HBB had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables.Results: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), Codons 8/9 (4.79%), Codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.9...
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).
2014
Thalassemia is one of the most common monogenic disorders, with a high demand for carrier detection and prenatal diagnosis in the Iranian population. In view of the presence of a large number of mutations associated with the disease, the polymorphic markers present in the β-globin gene cluster region were commonly used in linkage analysis of the disease. Markers usually show a population-based dependent haplotype frequency. Among the polymorphic markers, five markers including AvaII, RsaI, HinfI, TaqI and Hind III were genotyped in 150 unrelated healthy individuals from the Iranian population. The haplotype frequency was estimated using PHASE program and linkage disequilibrium (LD) was analyzed by MIDAS program. Among the eight possible haplotypes, five haplotypes showed relatively high frequencies (≥ 5%), of which the haplotype AvaII-TaqI-HindIII with the highest frequency could be suggested as an informative haplotype for possible carrier detection and prenatal diagnosis of beta thalassemia in the Iranian population. Moreover, the LD results showed that RsaI and HinfI (located in the hotspot region) were not associated with the 5' sub-haplotypes or 3' sub-haplotypes, and therefore, these markers might be excluded as strong molecular diagnostic markers in beta globin gene region in the Iranian population.