Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?

Background: Unlike in adults, there is no consensus on management and diagnosis of polycythemia in children. This study aims to evaluate the diagnosis and verify the algorithm in children with polycythemia. Methods: Seventy-nine children with polycythemia were followed-up in our pediatric hematology...

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Main Authors: Hatice Mine Cakmak, Omer Kartal, Ayca Kocaaga, Yasar Bildirici
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Pediatrics and Neonatology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1875957222001589
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author Hatice Mine Cakmak
Omer Kartal
Ayca Kocaaga
Yasar Bildirici
author_facet Hatice Mine Cakmak
Omer Kartal
Ayca Kocaaga
Yasar Bildirici
author_sort Hatice Mine Cakmak
collection DOAJ
description Background: Unlike in adults, there is no consensus on management and diagnosis of polycythemia in children. This study aims to evaluate the diagnosis and verify the algorithm in children with polycythemia. Methods: Seventy-nine children with polycythemia were followed-up in our pediatric hematology-oncology clinic between December 15, 2019, and July 15, 2021. After eliminating secondary causes (hypoxia, pulmonary, cardiac diseases), we checked for genetic mutations, including congenital erythrocytosis gene panel (JAK, EPOR, EPAS1, EGNL1, HBB, HBA, BPGM, and VHL). We also compared parameters for secondary and idiopathic polycythemia groups. Results: Of the 79 children, thirty-five had secondary polycythemia (hypoxia, pulmonary, cardiac diseases), and one was diagnosed with a novel likely pathogenic mutation c.2089C  >  G; p.Pro697Ala in exon 13 of EPAS1 gene. Others (n = 35) had persistent and idiopathic polycythemia. Here, we compared the idiopathic and secondary cases. We found that the ratio of family history of polycythemia (n = 4 (9.5%) vs 0%, respectively) was higher in the second group (p = 0.009). In addition, the mean age (14.7 ± 3.52 vs 13.4 ± 4.67 respectively) (p = 0.042) and the ratio of erythroid hyperplasia in bone marrow [n = 3 (8.6%) vs 0% respectively] (p = 0.003) was higher in the idiopathic polycythemia group, compared to secondary polycythemia patients. Conclusion: Finding the genetic defect in polycythemia is a significant issue. Due to being a rarity in children, the first line JAK mutation analysis should be performed in selected cases. This study is the first description of a Turkish patient with EPAS1 p.Pro697Ala mutation, thereby expanding our knowledge about the clinical features of the disease. However, new investigations are required to confirm its function.
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spelling doaj-art-06eebe63a20f4a7b8e2f9b69cedf0ffa2025-08-20T02:02:51ZengElsevierPediatrics and Neonatology1875-95722022-11-0163661361710.1016/j.pedneo.2022.06.006Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?Hatice Mine Cakmak0Omer Kartal1Ayca Kocaaga2Yasar Bildirici3Duzce University Pediatric Hematology-Oncology, Duzce, Turkey; Corresponding author.Gulhane Research and Training Hospital, Department of Pediatric Hematology-Oncology, Ankara, TurkeyEskisehir City Hospital, Department of Genetics, Eskisehir, TurkeyEskisehir City Hospital, Department of Pediatrics, Eskisehir, TurkeyBackground: Unlike in adults, there is no consensus on management and diagnosis of polycythemia in children. This study aims to evaluate the diagnosis and verify the algorithm in children with polycythemia. Methods: Seventy-nine children with polycythemia were followed-up in our pediatric hematology-oncology clinic between December 15, 2019, and July 15, 2021. After eliminating secondary causes (hypoxia, pulmonary, cardiac diseases), we checked for genetic mutations, including congenital erythrocytosis gene panel (JAK, EPOR, EPAS1, EGNL1, HBB, HBA, BPGM, and VHL). We also compared parameters for secondary and idiopathic polycythemia groups. Results: Of the 79 children, thirty-five had secondary polycythemia (hypoxia, pulmonary, cardiac diseases), and one was diagnosed with a novel likely pathogenic mutation c.2089C  >  G; p.Pro697Ala in exon 13 of EPAS1 gene. Others (n = 35) had persistent and idiopathic polycythemia. Here, we compared the idiopathic and secondary cases. We found that the ratio of family history of polycythemia (n = 4 (9.5%) vs 0%, respectively) was higher in the second group (p = 0.009). In addition, the mean age (14.7 ± 3.52 vs 13.4 ± 4.67 respectively) (p = 0.042) and the ratio of erythroid hyperplasia in bone marrow [n = 3 (8.6%) vs 0% respectively] (p = 0.003) was higher in the idiopathic polycythemia group, compared to secondary polycythemia patients. Conclusion: Finding the genetic defect in polycythemia is a significant issue. Due to being a rarity in children, the first line JAK mutation analysis should be performed in selected cases. This study is the first description of a Turkish patient with EPAS1 p.Pro697Ala mutation, thereby expanding our knowledge about the clinical features of the disease. However, new investigations are required to confirm its function.http://www.sciencedirect.com/science/article/pii/S1875957222001589a novel EPAS1 mutationchildrenidiopathicpolycythemia
spellingShingle Hatice Mine Cakmak
Omer Kartal
Ayca Kocaaga
Yasar Bildirici
Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?
Pediatrics and Neonatology
a novel EPAS1 mutation
children
idiopathic
polycythemia
title Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?
title_full Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?
title_fullStr Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?
title_full_unstemmed Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?
title_short Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutationWhat is knownWhat is new?
title_sort diagnosis and genetic analysis of polycythemia in children and a novel epas1 gene mutationwhat is knownwhat is new
topic a novel EPAS1 mutation
children
idiopathic
polycythemia
url http://www.sciencedirect.com/science/article/pii/S1875957222001589
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