Genotype-Phenotype Correlation of Hereditary Erythrocytosis Mutations, a single center experience.

Autor: Oliveira JL; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Coon LM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Frederick LA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Hein M; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Swanson KC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Savedra ME; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Porter TR; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Patnaik MM; Department of Hematology and Oncology, Mayo Clinic, Rochester, MN., Tefferi A; Department of Hematology and Oncology, Mayo Clinic, Rochester, MN., Pardanani A; Department of Hematology and Oncology, Mayo Clinic, Rochester, MN., Grebe SK; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Viswanatha DS; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Hoyer JD; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2018 May 23. Date of Electronic Publication: 2018 May 23.
DOI: 10.1002/ajh.25150
Abstrakt: Hereditary erythrocytosis is associated with high oxygen affinity hemoglobin variants (HOAs), 2,3-bisphosphoglycerate deficiency and abnormalities in EPOR and the oxygen-sensing pathway proteins PHD, HIF2α, and VHL. Our laboratory has 40 years of experience with hemoglobin disorder testing and we have characterized HOAs using varied protein and molecular techniques including functional assessment by p50 analysis. In addition, we have more recently commenced adding the assessment of clinically relevant regions of the VHL, BPGM, EPOR, EGLN1 (PHD2), and EPAS1 (HIF2A) genes in a more comprehensive hereditary erythrocytosis panel of tests. Review of our experience confirms a wide spectrum of alterations associated with erythrocytosis which we have correlated with phenotypic and clinical features. Through generic hemoglobinopathy testing we have identified 762 patients with 81 distinct HOA Hb variants (61 β, 20 α), including 12 that were first identified by our laboratory. Of the 1192 cases received for an evaluation specific for hereditary erythrocytosis, approximately 12% had reportable alterations: 85 pathogenic/likely pathogenic mutations and 58 variants of unknown significance. Many have not been previously reported. Correlation with clinical and phenotypic data supports an algorithmic approach to guide economical evaluation; although, testing is expanded if the suspected causes are negative or of uncertain significance. Clinical features are similar and range from asymptomatic to recurrent headaches, fatigue, restless legs, chest pain, exertional dyspnea and thrombotic episodes. Many patients were chronically phlebotomized with reported relief of symptoms. This article is protected by copyright. All rights reserved.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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