Hereditary gene mutations in Korean patients with isolated erythrocytosis

Abstract

Most cases of erythrocytosis occur secondary to chronic tissue hypoxia or as a clonal disease such as polycythemia vera with somatic mutations in the Janus kinase 2 (JAK2) gene. Rarely, erythrocytosis is caused by hereditary gene mutations. This study investigated hereditary gene mutations in 38 unrelated Korean patients with isolated erythrocytosis without (1) JAK2 mutation and (2) secondary causes of erythrocytosis other than smoking history. Direct sequencing analyses were performed on six genes associated with hereditary erythrocytosis [HBB, exon 2 and exon 3 of HBA2, VHL, EGLN1 (previously PHD2), exon 12 of EPAS1 (previously HIF2A), and exons 5-8 of EPOR]. As a result, mutations were detected in five patients (three never smokers and two current smokers) out of 38 patients (13.2 %). The mutations detected in those five patients were EPOR:p.W439*, EPOR:p.G212C, HBB:p.H98Q (or conventionally H97Q, Hb Malmö [β 97(FG4) His > Gln]), HBB:p.V138M (V137M), and EGLN1:p.L279Tfs43*, all in heterozygous state. No patient had mutations in HBA2, VHL, or in EPAS1. This study indicates that workup for hereditary gene mutations is needed for isolated erythrocytosis with or without smoking history.

Gene panel sequencing improves the diagnostic work-up of patients with idiopathic erythrocytosis and identifies new mutations

“…EGLN1 p.L279P affects a conserved residue, previously reported as altered (p.L279Tfs43, a frameshift variant) in a patient with erythrocytosis. 20 Structurally, this 12 47 …”

Hb Heathrow [β103(G5)Phe→Leu], a First Report in an Asian Patient with Erythrocytosis

“…For example, Bento, et al8 reported that only 25 of 70 patients (36%) had a known causative gene defect. Similarly, only 13.2 % of Korean patients with erythrocytosis had a known causative gene mutation 6. Therefore, further studies are needed to identify the new genetic cause of erythrocytosis.…”

“…Congenital (familial) erythrocytosis was suspected. We performed alpha 1-globin gene ( HBA1 )/alpha 2-globin gene ( HBA2 ), beta-globin gene ( HBB ), and Von Hippel Lindau ( VHL ) gene mutation analysis according to a previous study 6. All coding sequences and flanking intronic regions of HBA1/HBA2 , HBB , and VHL were analyzed.…”

Guidelines for the management of myeloproliferative neoplasms

“…Lastly, it is important to rule out a hereditary background [ 23 ]. Recent data in Korea revealed a significant proportion (13.2%) of patients with JAK2 -negative idiopathic isolated erythrocytosis had germline mutations [ 24 ].…”

“…The NHI program covers the entire Korean population as a compulsory social insurance system. Age-standardized incidence rates are estimated by calculating weighted averages of crude age-specific rates, using the mid-year estimated population of Korea in the year 2000 as the standard population, and calculated using the world standard population as the reference population [ 24 ].…”