The Spectrum of β-Thalassemia Mutations in Hatay, Turkey: Reporting Three New Mutations

Aldemir, Ozgur; İzmirli, Müzeyyen; Kaya, Hasan

doi:10.3109/03630269.2014.944915

Cited by 9 publications

(4 citation statements)

References 19 publications

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“…The wide molecular heterogeneity of Turkish thalassemic subjects has been confirmed by this registry. The most common seven mutations accounted for less than 80% of all thalassemia alleles, consistent with previous reports from Turkey [ 15 , 16 , 17 , 18 , 19 , 20 ]. The IVS-I-110(G->A) substitution was the most common defect with a frequency of 47% within all b-thalassemia alleles in the cohort.…”

Section: Discussionsupporting

confidence: 91%

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention

Aydınok

Oymak

Atabay

et al. 2018

Tjh

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Objective:The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey.Materials and Methods:A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with β-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%).Results:The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all β-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999.Conclusion:While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

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Section: Discussionsupporting

confidence: 91%

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention

Aydınok

Oymak

Atabay

et al. 2018

Tjh

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“…The most common mutations were: IVS-I-110 (G > A), IVS-I-6 (T > C), IVS-I-1 (G > A), frameshift codon (FSC)8(ÀAA), codon 39 (C > T), and IVS-II-745 (C > G). They reported that many Syrian and Iraqi immigrants presented with a prevalence of thalassemia traits that were different from other studies [2]. β-Thalassemia is caused by more than 300 different β-globin chains (http:// www.ithanet.eu/db/ithagenes;http://globin.bx.psu.edu/hbvar) but only about 40 account for 90% or more of β-thalassemia cases worldwide [6].…”

Section: Molecular Diagnosis Of β-Thalassemiamentioning

confidence: 92%

“…βThalassemia in the group of thalassemia syndromes is molecularly heterogeneous. Especially, genetic testing can provide important information fordiagnosis,treatment,andprevention.There are some limitations to genetic testing in all types of thalassemia; the most important issue is to find the right patient on which to perform genetic testing [2].…”

Section: Introductionmentioning

confidence: 99%

The Genetic Aspect of Thalassemia: From Diagnosis to Treatment

Aldemir¹

2018

Thalassemia and Other Hemolytic Anemias

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Hemoglobinopathies are a group of red blood cell productivity disorders, including α-thalassemia, β-thalassemia, and sickle cell disease (SCD), that are autosomal recessive and very common in Mediterranean, Middle Eastern, East Asian, and African countries. Thalassemia presents with the following clinical signs and symptoms: fatigue, weakness, yellowish skin, facial bone deformities, and abdominal swelling. Genetic studies have successfully characterized the key variants and pathways involved in hemoglobin F (HbF) regulation, providing new therapeutic targets for HbF reactivation. According to the current literature, using lentivirus vector for gene therapy and genome-editing-based treatment strategies for β-thalassemia and SCD have been discussed and well documented. According to current studies, novel treatments are becoming more important for thalassemia patients, because the consequences of supportive treatments are not sufficient for patients and their families. Supportive treatment does not have a positive effect on the survival rate of β-thalassemia patients. New treatments are empowering to develop develop a gene therapy for β-thalassemia and include pharmacological or disruption of BCL11A erythroid enhancer by CRISPR-CAS9 technology in addition to zinc-finger or transcription activator-like effector nuclease, and attempts at repairing the defective β-globin gene in hematopoietic stem cells by genome editing. These approaches are needed to improve for being more successful; gene addition has the advantage of making use of a single product applicable to all cases of β-thalassemia.

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“…The IVS-I-6 (T→C) mutation is one of the most common causes of β-thalassemia among individuals of Mediterranean and Middle Eastern ancestry [39,40]. Its high incidence has been reported among populations from Portugal [41]; Spain [42,43]; Albania [44]; the region of former Yugoslavia [45,46,47,48]; Greece [49,50,51,52]; Algeria [53]; Egypt [54]; Palestine [55,56]; Lebanon [57]; Syria [58,59]; Cyprus [60]; Turkey [61,62,63,64,65]; Saudi Arabia [66,67]; Iraq [68,69,70,71]; Iran [72,73,74]; and elsewhere. It results from a base substitution close to the 5′ splice junction, between exon I and intron I, and within a conserved consensus sequence, interfering with mRNA splicing and, consequently, reducing its efficiency.…”

Section: Discussionmentioning

confidence: 99%

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence

et al. 2017

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Extramedullary hematopoiesis (EMH) results from the extension of hematopoietic tissue beyond the confines of the bones. Since the initiation of regular transfusion programs from an early age for all thalassemia major (ΤΜ) patients, EMH has not been considered a clinical issue anymore. The present study aims to record the prevalence of EMH in chronically transfused ΤΜ patients followed at our institution and to investigate possible risk factors associated with its occurrence. The project was designed as a retrospective, nonexperimental, descriptive, exploratory study. In total, the study enrolled 104 patients. EMH was revealed in 15/104 (14%) patients. The presence of intravening sequence (IVS)-I-6 was significantly related with the development of EMH (p < 0.05). No other demographic or biological factor studied was found to be related with the presence of EMH. The study stresses a profound incidence of asymptomatic EMH in a solid group of well-transfused ΤΜ patients. Given the high incidence of the IVS-I-6 allele in the Mediterranean and Middle Eastern region, high-quality, prospective, multicenter studies could confirm the association of EMH occurrence with the presence of the IVS-I-6 mutation and further evaluate the exact role of this mutation in the EMH process.

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The Spectrum of β-Thalassemia Mutations in Hatay, Turkey: Reporting Three New Mutations

Cited by 9 publications

References 19 publications

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention

The Genetic Aspect of Thalassemia: From Diagnosis to Treatment

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence

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