Utility of next-generation sequencing in identifying congenital erythrocytosis in patients with idiopathic erythrocytosis

Anžej Doma, Saša (author), Kraljić, Nika (author), Kristan, Aleša (author), Debeljak, Nataša (author), Maver, Aleš (author), Pajič, Tadej (author), Preložnik Zupan, Irena (author)

Background: Congenital erythrocytosis (CE) is increasingly recognized as the cause of erythrocytosis in patients in whom polycythemia vera and secondary acquired causes have been excluded. The aim of our study was to determine possible genetic background in patients with idiopathic erythrocytosis. Methods: 40 patients with idiopathic erythrocytosis, referred to our institution in a 5-year period, were analyzed. We collected data on erythropoietin (Epo) levels, hemoglobin (Hgb), hematocrit (Hct), erythrocyte count, age, gender, past thrombotic events, concomitant diseases, and smoking status. CE was tested using next-generation sequencing (NGS), in the majority of patients also measurement of P50 and Hgb electrophoresis were performed. Patients with signs of iron overload were tested for genetic variants in the HFE gene. Results: The median patient age at analysis was 46.5 years (range 22–73), with 37 out of 40 being males (93 %). The median Hgb, Hct and red blood cells count were 180 g/L, 0.51, 5.985 x 10$^{12}$/L in men and 171 g/L, 0.50 and 5.68 x 10$^{12}$/L in women, respectively. Epo levels were decreased in three, increased in one patient and within the normal range in the rest (median 7.55 mIU/mL; range 2.90–19.50). Eight patients (20 %) smoked. 32 (80 %) were treated with low-dose aspirin, and 20 (50 %) underwent at least one phlebotomy. Thromboembolic events were recorded in 2 patients (5 %). P50 was measured in 20 out of 40 patients, and it was above 24 mm Hg (3.12 kPa) in all of them. Hemoglobin electrophoresis was performed in 73 % of patients, with no abnormal Hgb detected. Variants in the HFE gene were found in 8 out of 40 patients (20 %), but in only one patient the results were associated with an increased risk for hemochromatosis. Although no pathogenic variants for CE were detected by NGS, two variants of uncertain significance, namely EGLN1 (NM_022051.2):c.1072C>T (p.(Pro358Ser)) and EGLN1 (NM_022051.2):c.1124A>G (p.(Glu375Gly)) were identified as strong etiologic candidates. Conclusion: CE is an extremely rare condition. Genetic testing is advised in young individuals with a long-standing persistent erythrocytosis, possibly with a family history and after exclusion of more frequent secondary causes and polycytemia vera.

• Language: English
• Keywords: non-clonal erythrocytosis, congenital erythrocytosis, next-generation sequencing, erythropoietin, hemochromatosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 8 str.
• Numbering: Vol. 11, art. 1440712
• PID: 20.500.12556/RUL-164993
• UDC: 61:577.2
• ISSN on article: 2296-858X
• DOI: 10.3389/fmed.2024.1440712
• COBISS.SI-ID: 207664387
• Publication date in RUL: 20.11.2024

ANŽEJ DOMA, Saša, KRALJIĆ, Nika, KRISTAN, Aleša, DEBELJAK, Nataša, MAVER, Aleš, PAJIČ, Tadej and PRELOŽNIK ZUPAN, Irena, 2024, Utility of next-generation sequencing in identifying congenital erythrocytosis in patients with idiopathic erythrocytosis. Frontiers in medicine [online]. 2024. Vol. 11, no. 1440712. [Accessed 24 April 2025]. DOI 10.3389/fmed.2024.1440712. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=164993

Record is a part of a journal

• Title: Frontiers in medicine
• Shortened title: Front. med.
• Publisher: Frontiers Media S.A.
• ISSN: 2296-858X
• COBISS.SI-ID: 523095065

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: neklonska eritrocitoza, prirojena eritrocitoza, sekvenciranje naslednje generacije, eritropoetin, hemokromatoza