The molecular spectrum and distribution of haemoglobinopathies in Cyprus: a 20-year retrospective study

Kountouris, Petros; Kousiappa, Ioanna; Papasavva, Thessalia; Christopoulos, George; Pavlou, Eleni; Petrou, Miranda; Feleki, Xenia; Karitzie, Eleni; Phylactides, Marios; Fanis, Pavlos; Lederer, Carsten W.; Kyrri, A.; Kalogerou, Eleni; Makariou, Christiana; Ioannou, Christiana; Kythreotis, Loukas; Hadjilambi, Georgia; Andreou, Nicoletta; Pangalou, Evangelia; Savvidou, Irene; Angastiniotis, Michael; Hadjigavriel, Michael; Sitarou, Maria; Kolnagou, Annita; Kleanthous, Marina; Christou, Soteroula

doi:10.1038/srep26371

Cited by 42 publications

(38 citation statements)

References 27 publications

(48 reference statements)

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“…All family members were genotypically screened for the presence of mutations at the HBA1 , HBA2 ( α‐globin ), and HBB ( β‐globin ) genes as described before (Kountouris et al, ). For the investigation of the unusually high levels of HbF, we sequenced (Sanger sequencing) the KLF1 gene (promoter region, 5′‐UTR, coding region, flanking splice junctions, and 238 bp of the 3′‐UTR) and the promoter regions of the HBG1 and HBG2 ( γ‐globin ) genes.…”

Section: Design and Methodsmentioning

confidence: 99%

A novel mutation in the erythroid transcription factor KLF1 is likely responsible for ameliorating β‐thalassemia major

et al. 2019

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We describe the identification of a novel missense mutation in the second zinc finger of KLF1 in two siblings who, based on their genotype, are predicted to suffer from beta thalassemia major but are, in fact, transfusion‐free and in good health. These individuals, as well as two additional members of the same family also carrying this KLF1 mutation, exhibit high levels of fetal hemoglobin (HbF). KLF1 is an erythroid transcription factor, which plays a critical role in the regulation of the developmental switch between fetal and adult hemoglobin by regulating the expression of a multitude of genes including that of BCL11A. The mutation appears to be the main candidate responsible for the beta thalassemia‐ameliorating effect as this segregates with the observed phenotype and also exogenous expression of the KLF1 mutant protein in human erythroid progenitor cells resulted in the induction of γ‐globin, without, however, affecting BCL11A levels. This report adds to the weight of evidence that heterozygous KLF1 mutations can ameliorate the severity of the β‐thalassemia major phenotype.

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Section: Design and Methodsmentioning

confidence: 99%

A novel mutation in the erythroid transcription factor KLF1 is likely responsible for ameliorating β‐thalassemia major

et al. 2019

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“…A European Haemoglobinopathy Registry could enhance monitoring of changing demographics, service delivery and patient outcomes, and improve patient access to care (Inusa & Colombatti, ). Of the countries that participated in the conference, national registries for SCD exist in Belgium, Cyprus, Germany, Greece, Spain and the UK (Cela et al , ; Kountouris et al , ; Kunz et al , ; Le et al , ; Voskaridou et al , ; http://nhr.mdsas.com/).…”

Section: Resultsmentioning

confidence: 99%

“…Streetly (2000Streetly ( , 2005 Streetly et al (2008,2010,2018) Please note: The UK has a linked antenatal and neonatal screening programme for haemoglobinopathies. Cyprus and Turkey have antenatal programmes only (Angastiniotis & Hadjiminas, 1981;Kolnagou & Kontoghiorghes, 2009;Canatan, 2014;Kountouris et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Newborn screening for sickle cell disease in Europe: recommendations from a Pan‐European Consensus Conference

et al. 2018

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Summary Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two‐day Pan‐European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus‐based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes.

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“…Notable differences were found in the frequencies of different mutations between the four districts in this small island, and several mutations were being reported for the first time in this population. This is the first study where a comprehensive molecular analysis of all the β thalassemia patients and Hb H disease patients has been done …”

Section: Discussionmentioning

confidence: 99%

“…This is the first study where a comprehensive molecular analysis of all the β thalassemia patients and Hb H disease patients has been done. 60 In a vast and ethnically diverse country like India, molecular analysis of the different globin genes of all patients with hemoglobinopathies is an impossible task due to the very large numbers.…”

Section: Many Of the Uncommon β Chain Hemoglobin Variants Likementioning

confidence: 99%

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

Nadkarni

Gorakshakar

Sawant

et al. 2018

Int J Lab Hematology

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Introduction The hemoglobinopathies pose a significant health burden in India. Apart from the β thalassemias and sickle cell disorders, α thalassemias and structural hemoglobin variants are also common. Here we have reviewed the phenotypic and molecular diversity of hemoglobinopathies encountered at a referral center in western India over a period of 15 years. Materials and Methods Screening for hemoglobinopathies was done using HPLC and cellulose acetate electrophoresis. Molecular characterization was done using Covalent Reverse Dot Blot Hybridization (CRDB), Amplification Refractory Mutation System (ARMS), GAP PCR and direct DNA sequencing. Results The study includes 31 075 individuals who were referred for diagnosis of hemoglobinopathies and prenatal diagnosis. Of these 14 423 individuals showed various hemoglobin abnormalities. Beta genotyping in 5615 individuals showed the presence of 49 β thalassemia mutations. 143 β thalassemia heterozygotes had normal or borderline HbA2 levels. We identified three δ gene mutations (HbA2 Pellendri, HbA2 St.George, HbA2 Saurashtra) in β thalassemia heterozygotes leading to normal HbA2 levels. The commonest defects among the raised Hb F determinants were Gγ(Αγδβ)0 Indian inversion and the HPFH‐3 Indian deletion. A total of 312 individuals showed the presence of α thalassemia, of which 12.0% had a single α gene deletion (−α/αα). HbH disease was identified in 29 cases with 10 different genotypes. Alpha globin gene triplication was seen in 2.1% of β thalassemia heterozygotes with a thalassemia intermedia phenotype. Seven unusual α chain variants and eight uncommon β chain variants were identified. Conclusion The repertoire of molecular defects seen in the different globin genes will be valuable for management and control of these disorders both in India as well as in other countries where there is a huge influx of migrant populations from India.

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The molecular spectrum and distribution of haemoglobinopathies in Cyprus: a 20-year retrospective study

Cited by 42 publications

References 27 publications

A novel mutation in the erythroid transcription factor KLF1 is likely responsible for ameliorating β‐thalassemia major

A novel mutation in the erythroid transcription factor KLF1 is likely responsible for ameliorating β‐thalassemia major

Newborn screening for sickle cell disease in Europe: recommendations from a Pan‐European Consensus Conference

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

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