Genetic Analysis of Three Iranian Patients with Unexplained Absolute Erythrocytosis Using Customized Gene Panel Sequencing: A Case Series
Gene Panel Sequencing in Erythrocytosis
Keywords:
Polycythemia, Erythrocytosis, High-throughput nucleotide sequencing, Genetic variationAbstract
Introduction:Erythrocytosis is a medical condition characterized by an increased mass of red blood cells, typically indicated by elevated levels of hemoglobin and hematocrit. This case series underscores the diagnostic challenge presented by unexplained absolute erythrocytosis in patients lacking canonical driver mutations and highlights the importance of utilizing extended gene panels to detect rare variants associated with erythropoiesis.
Case Report: Three Iranian patients exhibited absolute erythrocytosis, characterized by elevated hemoglobin and hematocrit levels, a normal erythropoietin concentration, and no history of smoking or chronic hypoxia. In addition, one female patient had coronary artery disease and mild hepatosplenomegaly, while the other two male patients were asymptomatic. Patients were referred from Ali Ebne Abitaleb Hospital in Zahedan to Dr. Kordi’s Medical Genetics Laboratory in Zahedan for genetic assessments. Canonical genetic mutation analysis using Sanger sequencing revealed no mutations in hotspot regions of JAK2, CALR, and MPL (triple-negative). Therefore, targeted next-generation sequencing (NGS) was performed for these three patients using a customized 504-gene panel to identify potential genetic variants. After that, three rare missense variants were identified using a standard NGS analysis pipeline: NM_022162.3(NOD2):c.743T>G:p.Leu248Arg (rs104895423), NM_000402.4(G6PD):c.1039G>A:p.Glu347Lys (rs5030872), and NM_144658.3(DOCK11):c.2762G>A:p.Arg921Gln (rs2014585801). These variants were indexed as variants of uncertain significance (VUS) by the ClinVar and InterVar databases. Finally, variants were visualized using the Integrative Genomics Viewer (IGV) software.
Conclusion: These findings indicate that rare variants in our patients may contribute to unexplained absolute erythrocytosis.
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