β-Thalassemia intermedia in a lebanese child due to homozygosity for the -88 (C→T) Mutation

Waye, JS; Patterson, Michael M.; Mf, Scully

doi:10.3109/03630269409045770

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…Twenty different β‐thalassemia mutations were identified, of which the frameshift at cd 36/37 (−T) had never been reported before in Lebanon. In addition, four previously described (Chehab et al 1987; Waye et al 1994; Zahed et al 1997) mutations have not been identified in our subjects; these mutations were the IVS‐II‐1 (G>T) substitution, the C>G substitution at position −86, the T>A transversion at position –30, and finally the G>A change at cd 30. If these mutations are included, the number of β‐thalassemia mutations found in the Lebanese population is 24, reflecting an even more heterogeneous population than previously described.…”

Section: Discussionmentioning

confidence: 72%

Genetic Heterogeneity of Beta Thalassemia in Lebanon Reflects Historic and Recent Population Migration

Makhoul

Wells

Kaspar

et al. 2005

Annals of Human Genetics

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SummaryBeta thalassemia is an autosomal recessive disorder characterized by reduced (β + ) or absent (β 0 ) beta-globin chain synthesis. In Lebanon it is the most predominant genetic defect. In this study we investigated the religious and geographic distribution of the β-thalassemia mutations identified in Lebanon, and traced their precise origins. A total of 520 β-globin chromosomes from patients of different religious and regional backgrounds was studied. Beta thalassemia mutations were identified using Amplification Refractory Mutation System (ARMS) PCR or direct gene sequencing.Six (IVS-I-110, IVS-I-1, IVS-I-6, IVS-II-1, cd 5 and the C>T substitution at cd 29) out of 20 β-globin defects identified accounted for more than 86% of the total β-thalassemia chromosomes. Sunni Muslims had the highest β-thalassemia carrier rate and presented the greatest heterogeneity, with 16 different mutations. Shiite Muslims followed closely with 13 mutations, whereas Maronites represented 11.9% of all β-thalassemic subjects and carried 7 different mutations. RFLP haplotype analysis showed that the observed genetic diversity originated from both new mutational events and gene flow from population migration. This study provides information about the types and distribution of β-thalassemia mutations within each religious group and geographic region, which is essential for the implementation of screening and prevention programs.

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Section: Discussionmentioning

confidence: 72%

Genetic Heterogeneity of Beta Thalassemia in Lebanon Reflects Historic and Recent Population Migration

Makhoul

Wells

Kaspar

et al. 2005

Annals of Human Genetics

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“…The propositus in this family was homozygous for the −88 (C→T) mutation. Haplotype analysis of this family had suggested a possibility that the −88 (C→T) mutation might have a common origin in Lebanese and Asian Indian subjects (Waye et al. , 1994).…”

Section: Resultsmentioning

confidence: 94%

“…The propositus in this family was homozygous for the )88 (C fi T) mutation. Haplotype analysis of this family had suggested a possibility that the )88 (C fi T) mutation might have a common origin in Lebanese and Asian Indian subjects (Waye et al, 1994). The )88 (C fi T) mutation occurs very rarely among the Asian Indian population accounting for <0.5% of the mutant alleles (Colah & Gorakshakar, 2000).…”

Section: Resultsmentioning

confidence: 96%

An interplay of alleviating mutations in the clinical phenotype of beta-thalassaemia intermedia

Nadkarni

Sakaguchi²,

Gorakshakar

et al. 2004

Clin Lab Haematol

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Prediction of a beta-thalassaemia major phenotype from the beta-genotype is generally relatively straightforward. However, despite the ability to accurately define the beta-thalassaemia mutations, prediction of a beta-thalassaemia intermedia phenotype from the genotype sometimes remains problematic and this has important implications in genetic counselling and prenatal diagnosis. We report a 11-year-old Indian male child with a thalassaemia intermedia phenotype. beta-Globin gene analysis of the family showed that he was a compound heterozygote with the -88 (C-->T) beta+-mutation and the IVS1 nt 130 (G-->C) beta0-mutation. Both these mutations are rare among Indians. The propositus was also found to be heterozygous for the XmnI polymorphism and had a normal alpha-genotype. In this family interplay of two alleviating mutations (a milder promoter mutation along with a gene for raised HbF) might have synergistically compensated for lack of globin chains in the patient. Hence, the nature of the beta-genotype as well as the knowledge of the presence or absence of alleviating factors will help the clinician to decide whether early commencement of a regular transfusion regime is necessary.

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Molecular and population genetic analyses of β-Thalassemia in Turkey

et al. 1998

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In this report we describe the molecular analysis of 795 chromosomes derived from unrelated Turkish ␤-thalassemia and sickle cell anemia carriers identified in hematology clinics in Istanbul, Ankara, Izmir, Adana, and Antalya. The determination of the molecular pathology of 754 ␤-thalassemia and 42 abnormal hemoglobin genes and analysis of the frequency distribution in six distinct regions of Turkey was accomplished. The experimental strategy, based on PCR amplification of the ␤-globin gene, included dot-blot hybridization with 18 probes specific for the Mediterranean populations, denaturing gradient gel electrophoresis, and genomic sequencing. When the regional results are compared with the overall frequency of mutations in the country, it is observed that the frequencies in the western and southern parts of Turkey are in good accordance with the overall distribution, whereas the northern and eastern parts have a more region/ population-specific profile with some rare mutations having a significantly high occurrence in these regions. Further evaluation of the data with respect to region-or population-dependent differences will contribute to a better understanding of the mechanisms leading to the marked genetic heterogeneity in Turkey, but could also be extremely valuable in facilitating rapid identification of mutations in families at risk for different hemoglobinopathies. Am. J. Hematol. 57:215-220, 1998.

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β-Thalassemia intermedia in a lebanese child due to homozygosity for the -88 (C→T) Mutation

Cited by 5 publications

References 9 publications

Genetic Heterogeneity of Beta Thalassemia in Lebanon Reflects Historic and Recent Population Migration

Genetic Heterogeneity of Beta Thalassemia in Lebanon Reflects Historic and Recent Population Migration

An interplay of alleviating mutations in the clinical phenotype of beta-thalassaemia intermedia

Molecular and population genetic analyses of β-Thalassemia in Turkey

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