Genetic basis of congenital erythrocytosis

Bento, Celeste

doi:10.1111/ijlh.12828

Cited by 35 publications

(60 citation statements)

References 24 publications

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“…The exon 1 of EGLN1 ( PHD2 ) failed to amplify despite extensive optimization and various protocols, and it is possible that a few of the remaining four undiagnosed patients may have carried mutants of this gene. EGLN1 / PHD2 variants are classified as CE type 3 by OMIM, and all mutations found till date have been heterozygous with normal erythropoietin levels . Although our gene panel was carefully selected to comprehensively cover the previously described genetic defects, knowledge in the field continues to evolve.…”

Section: Discussionmentioning

confidence: 99%

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Genetic basis of unexplained erythrocytosis in Indian patients

Mallik

Sharma

Hira

et al. 2019

European J of Haematology

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Objective To evaluate the spectrum of genetic defects in Indian patients with unexplained erythrocytosis. Methods Fifteen families (18 patients) with unexplained erythrocytosis were enrolled after excluding polycythemia vera and secondary erythrocytosis. Focused Sanger sequencing from genomic DNA was performed for EPOR (exon 8), VHL (exons 2‐3), EGLN1 (exons 2‐5), EPAS1 (exon 12), and all exons of HBB, HBA1, and HBA2 genes. Results Eleven of the 18 patients (including two pairs of brothers) had Chuvash polycythemia, that is, homozygosity for VHL:c.598C > T (p.Arg200Trp). Three patients (two of whom were brothers) had HBB mutations associated with increased oxygen‐affinity hemoglobin—one had a heterozygous Hb McKees Rocks HBB:c.438T > A (p.Tyr146*), and two brothers showed heterozygous Hb Rainier HBB:c.437A > G (p.Tyr146Cys). No pathogenic variants were found in the remaining four cases. Conclusion A gene‐by‐gene Sanger sequencing approach could determine a genetic basis for erythrocytosis in 11 of the 15 (73%) Indian families, with homozygous VHL:c.598C > T (p.Arg200Trp) being the commonest pathogenic variant. This first study from the Indian subcontinent provides a rationale for analyzing this variant in patients with suspected congenital erythrocytosis from this region. Rare first occurrences of Hb McKees Rocks and Hb Rainier in Indians are also being reported.

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Section: Discussionmentioning

confidence: 99%

“…32 A recent review of CE suggested that next-generation sequencing based approach could be directly applied in suspected CE cases. 33…”

Section: An Abnormal Hplc Pattern Was Found In Only One Patient Withmentioning

confidence: 99%

Genetic basis of unexplained erythrocytosis in Indian patients

Mallik

Sharma

Hira

et al. 2019

European J of Haematology

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“…Yet, in the majority of patients with PV, a JAK2 mutation could be detected [7]. Thus, the diagnosis of a JAK2 mutation negative PV is very unusual and must always be questioned and congenital causes for erythrocytosis such as mutations in the EPO-receptor gene as well as mutations in the α-and β-globin-chains investigated [10]. Today and due to the improvement in molecular testing, congenital causes of erythrocytosis could be identified more easily [11].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, hyperviscosity symptoms and thromboembolic episodes have been reported and seem to be related to the high Hct. The higher affinity of O 2 to Hb leads to a lower oxygenation of tissues and consecutively to an erythrocytosis [10].…”

Section: Discussionmentioning

confidence: 99%

A Rare Hemoglobinopathy as a Cause of Erythrocytosis in a Patient with Suspected JAK2V617F Negative Polycythemia Vera: A Case Report

Jaekel¹,

Bauer²,

Behre³

et al. 2020

jmgm

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Introduction: Differential diagnosis of polyglobulia/erythrocytosis which is caused by deregulated erythropoiesis with an overproduction of red blood cells resulting in elevated hemoglobin and hematocrit levels is a diagnostic challenge. Case Report: A 31-year-old man was referred to us with a suspected diagnosis of polycythemia vera (a clonal myeloproliferative neoplasm) because of erythrocytosis. One year before, he suffered from an ischemic central retinal vein occlusion of unknown cause. Aspirin treatment was initiated. His mother was diagnosed with a JAK2V617F negative polycythemia vera years earlier and treated with phlebotomies as well as aspirin. Apart from erythrocytosis, laboratory analysis showed a normal white blood cell and platelet counts. The differential blood picture and lactate dehydrogenase were within the normal ranges. Molecular testing for BCR-ABL, JAK2V617F and Calreticulin gene mutations by PCR was negative. Bone marrow biopsy was normal without signs for a myeloproliferative neoplasm. As almost all patients with polycythemia vera carry the phenotype-driver mutation JAK2V617F, further genetic testing for congenital causes of erythrocytosis was conducted. Mutations in the EPO-receptor gene were not found, but a very rare heterozygous point mutation in the beta-globin-chain [exon 2 (c.119A>C) leading to a change in codon 40 (CAG>CCG)] was detected by next generation sequencing. This rare variant belongs to the high oxygen affinity hemoglobinopathies leading to a reduction of oxygen supply in tissues and an increase in red cell production. Conclusion: The diagnosis of a JAK2 mutation negative polycythemia vera must always be questioned and congenital causes of erythrocytosis excluded as the therapeutic and prognostic consequences are immense. Rare variants of hemoglobinopathies, particularly those with high oxygen affinity need to be excluded by molecular testing.

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“…Contemporary evaluation of erythrocytosis utilizes algorithms that help guide efficient testing for the majority of cases encountered in daily laboratory practice. [1][2][3][4][5] Because the most common causes of erythrocytosis are acquired, typical algorithmic entry points begin after investigations of a thorough clinical history, and exclusion of cardiac, pulmonary, and vascular disorders, and paraneoplastic conditions. Key algorithmic decision trees are based on serum erythropoietin (Epo) levels, and JAK2 genetic testing and oxygen dissociation (p50) results.…”

Section: Introductionmentioning

confidence: 99%

Algorithmic evaluation of hereditary erythrocytosis: Pathways and caveats

Oliveira

2019

Int J Lab Hematology

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Multiple algorithms have been published for the evaluation of hereditary erythrocytosis (HE). Typical entry points begin after excluding the more common acquired conditions through investigations of clinical history and assessment of cardiac, pulmonary, or vascular system disorders. Prior exclusion of JAK2 mutations, particularly the common JAK2 V617F mutation, is indicated in adults but less so in pediatric populations. Key decision trees are based on serum erythropoietin levels and p50 results. Recent data reveal some overlap in clinical presentation and laboratory findings in erythrocytosis. Caveats to consider when using algorithmic approaches are discussed.

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Genetic basis of congenital erythrocytosis

Cited by 35 publications

References 24 publications

Genetic basis of unexplained erythrocytosis in Indian patients

Genetic basis of unexplained erythrocytosis in Indian patients

A Rare Hemoglobinopathy as a Cause of Erythrocytosis in a Patient with Suspected JAK2V617F Negative Polycythemia Vera: A Case Report

Algorithmic evaluation of hereditary erythrocytosis: Pathways and caveats

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