Molecular characterization of β‐thalassaemia in 174 Greek patients with thalassaemia major

Kattamis, Christos; Hu, Hongbo; Cheng, George Z.; Reese, A. L.; Gonzalez‐Redondo, J. M.; Kutlar, Abdullah; Kutlar, Ferdane; Huisman, T. H. J.

doi:10.1111/j.1365-2141.1990.tb02593.x

Cited by 73 publications

(45 citation statements)

References 36 publications

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“…The IVS2-1 (G>A) mutation which is second in frequency in Jordan, has not been detected in Cyprus, Gaza, or Algeria but otherwise has a distribution pattern generally opposite to the distribution pattern of the IVS1-110 mutation in the region. In Jordan, this mutation has an intermediate frequency between the highest value reported for this mutation in Kuwait and Saudi Arabia and the lowest frequency reported in Syria and Greece [37,49]. 5.…”

Section: Discussionmentioning

confidence: 76%

Spectrum of β‐thalassemia in Jordan: Identification of two novel mutations

2001

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Two hundred and forty-four ␤-thalassemia alleles were identified from 135 unrelated occasionally and periodically transfusion dependent ␤-and S/␤-thalassemia patients from all regions of Jordan. Allele identification was achieved by PCR amplification of ␤-globin genes, dot-blotting the amplified DNA, hybridization with allele specific synthetic probes, and direct sequencing of amplified genomic DNA. A total of 19 different mutations were detected, eight of them constituted about 86% of the Jordanian thalassemic chromosomes. These mutations were IVS1-110 (G>A) (25%), IVS2-1 (G>A) (15%), IVS2-745 (C>G) (14.2%), IVS1-1 (G>A) (10%), IVS1-6 (T>C) (8.3%), codon 37 (G>A) (6.3%), codon 39 (C>T) (4.6%), and codon 5 (-C) (3.8%). The remaining eleven mutations were rare, presented with frequencies ranging between 0.4% and 1.6%. These included two novel mutations and four others detected in Jordan for the first time

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Section: Discussionmentioning

confidence: 76%

Spectrum of β‐thalassemia in Jordan: Identification of two novel mutations

2001

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“…In Greece, ϳ30 mutations have been observed, with 9 accounting for ϳ95% of ␤-thalassemia alleles, most of which are situated in the first half of the gene in close proximity (5,7,8 ) (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

“…In this study we report the standardization of a real-time detection method for most of the common ␤-thalassemia mutations throughout the world (5,6 ) along with the HbS mutation, using the Greek population as a model. In Greece, up to 10% of the population carry ␤-thalassemia or related hemoglobin variants, and ϳ30 pathologic point mutations in the ␤-globin gene (5)(6)(7)(8) have been observed, with 9 accounting for ϳ95% of the affected alleles (5,6 ). The method was rapid and accurate with high throughput for screening ␤-globin gene mutations in ␤-thalassemia heterozygotes.…”

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confidence: 99%

Rapid Screening of Multiple β-Globin Gene Mutations by Real-Time PCR on the LightCycler: Application to Carrier Screening and Prenatal Diagnosis of Thalassemia Syndromes

et al. 2003

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Background: Hemoglobinopathies are priority genetic diseases for prevention programs. Rapid genotype characterization is fundamental in the diagnostic laboratory, especially when offering prenatal diagnosis for carrier couples. Methods: As a model, we designed a protocol based on the LightCycler TM technology to screen for a spectrum of ␤-globin gene mutations in the Greek population. Design was facilitated by dual fluorochrome detection and close proximity of many mutations. Three probe sets were capable of screening 95% of ␤-globin gene mutations in the Greek population, including IVSII-745C3 G, HbS, Cd5-CT, Cd6-A, Cd8-AA, IVSI-1G3 A, IVSI-5G3 A, IVSI-6T3 C, IVSI-110G3 A, and Cd39 C3 T. Results: The protocol, standardized by analysis of 100 ␤-thalassemia heterozygotes with known mutations, was 100% reliable in distinguishing wild-type from mutant alleles. Subsequent screening of 100 Greek ␤-thalassemia heterozygotes with unknown mutations found 96 of 100 samples heterozygous for 1 of the 10 mutations, although melting curves were indistinguishable for mutations ⌯bS/Cd6 and IVSI-5/IVSI-1, indicating a need of alternative methods for definitive diagnosis. One sample demonstrating a unique melting curve was characterized by sequencing as Cd8/9؉G. Three samples carried mutations outside the gene region cov-

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“…The most widespread and common mutation among Arabs is the IVS-I-110 (G>A). The latter mutation has its highest prevalence in Cyprus and Greece (Baysal et al 1992;Kattamis et al 1990) giving the notion that it maybe of Greek origin. Among Arabs, this mutation is most frequent in Lebanon, Egypt, Syria, Jordan and parts of Saudi Arabia (Table 2), and it decreases in frequency as we move to the east where it becomes rare in the Eastern Arabian peninsula to be replaced by the Asian Indian mutations (IVS-I-5 (G>C), codons 8/9 (+G) and IVS-I (−25 bp del)) which are most common in Oman, UAE and Bahrain.…”

Section: Introductionmentioning

confidence: 99%

Epidemiological profile of common haemoglobinopathies in Arab countries

2012

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Haemoglobinopathies including the thalassemias and sickle cell disease are known to be prevalent inherited disorders in most Arab countries with varying prevalence rates and molecular characterisation. β-thalassemia is encountered in polymorphic frequencies in almost all Arab countries with carrier rates of 1-11 % and a varying number of mutations. The most widespread mutation in Lebanon, Egypt, Syria, Jordan, Tunisia and Algeria is the IVS-I-110 (G>A). In the Eastern Arabian Peninsula, the Asian Indian mutations (IVS-I-5 (G>C), codons 8/9 (+G) and IVS-I (−25 bp del)) are more common. The α-thalassemias are encountered in the majority of Arab countries in frequencies ranging from 1 to 58 % with the highest frequencies reported from Gulf countries. The (−α 3.7 ) mutation is the most frequent followed by the non-deletional α2 polyadenylation signal mutation (AATAAA>AATAAG) and the α2 IVS1 5-bp deletion. The rates of sickle cell trait in Arab countries range from 0.3 to 30 %, with the Benin, the Arab-Indian and the Bantu haplotypes constituting the bulk of the haplotypes, leading to two major phenotypes; a mild one associated with the Arab-Indian and a severe one with the Benin and Bantu haplotypes. Public health approaches targeting prevention of haemoglobinopathies in Arab countries include newborn screening for sickle cell disease, and premarital screening for carriers of β-thalassemia and sickle cell disease. These services are still patchy and inadequate in many Arab countries recommending the upgrade of these services with strengthening of the education and training of health care providers and raising public awareness on the feasibility of prevention and care for haemoglobinopathies.

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Molecular characterization of β‐thalassaemia in 174 Greek patients with thalassaemia major

Cited by 73 publications

References 36 publications

Spectrum of β‐thalassemia in Jordan: Identification of two novel mutations

Spectrum of β‐thalassemia in Jordan: Identification of two novel mutations

Rapid Screening of Multiple β-Globin Gene Mutations by Real-Time PCR on the LightCycler: Application to Carrier Screening and Prenatal Diagnosis of Thalassemia Syndromes

Epidemiological profile of common haemoglobinopathies in Arab countries

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