Essential Thrombocythemia Associated With Germline JAK2 G571S Variant and Somatic CALR Type 1 Mutation

Panovska-Stavridis, Irina; Eftimov, Aleksandar; Ivanovski, Martin; Pivkova-Veljanovska, Aleksandra; Čevreska, Lidija; Hermouet, Sylvie; Dimovski, Aleksandar

doi:10.1016/j.clml.2016.02.039

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…Pathogenic JAK2 variants can cause hereditary thrombocytosis and hereditary erythrocytosis with autosomal dominant inheritance. The JAK2 c.1711G>A, p.(Gly571Ser) variant detected here has already been described in the literature, not as clearly pathogenic, but in a somatic context in MPN [ 20 , 21 , 22 , 23 ]. In vitro assays did not reveal any changes in activity for this variant compared to the wild type [ 23 ] (ACMG criterion BS3).…”

Section: Resultsmentioning

confidence: 51%

NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients

Jalowiec

Vrotniakaite-Bajerciene

Capraru

et al. 2021

Genes

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(1) Background: Clinical and molecular data on patients with unexplained erythrocyto-sis is sparse. We aimed to analyze the clinical and molecular features of patients with congenital erythrocytosis in our tertiary reference center. (2) Methods: In 34 patients with unexplained erythrocytosis, a 13-gene Next-Generation Sequencing erythrocytosis panel developed at our center was conducted. (3) Results: In 6/34 (18%) patients, eight different heterozygous gene variants were found. These patients were, therefore, diagnosed with congenital erythrocytosis. Two patients had two different gene variants each. All variants were characterized as variants of unknown significance as they had not previously been described in the literature. The rest of the patients (28/34, 82%) had no detected gene variants. (4) Conclusions: Our experience shows that the NGS panel can be helpful in determining the reasons for persistent, unexplained erythrocytosis. In our cohort of patients with erythrocytosis, we identified some, thus far unknown, gene variants which may explain the clinical picture. However, further investigations are needed to determine the relationship between the molecular findings and the phenotype.

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Section: Resultsmentioning

confidence: 51%

NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients

Jalowiec

Vrotniakaite-Bajerciene

Capraru

et al. 2021

Genes

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“…The G571S mutation was found in only 3 samples, compared to the V617F mutation which was positive in 4280 samples. A recent report describes a family with germline G571S mutations [10], none of whom showed erythrocytosis. The G571S mutation was also found in two patients with “triple-negative” ET and PMF [9].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the limited penetrance [10] and in vitro studies [9], it is unlikely that the G571S mutation is the sole driver of erythropoiesis. We hope that this report will facilitate additional studies of patients with the G571S and related exon 13 JAK2 mutations, so as to ascertain their role in the pathogenesis of myeloproliferative disorders.…”

Section: Discussionmentioning

confidence: 99%

The role of the Exon 13 G571S JAK2 mutation in myeloproliferative neoplasms

Bahar

Barton

Kini

2016

Leukemia Research Reports

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The exon 14 JAK2 V617F mutation has been well established as a driver mutation in polycythemia vera (PV) and other myeloproliferative neoplasms. JAK2 exon 12 mutations have also been implicated in PV, although patients with these mutations may show isolated erythrocytosis. Recently additional JAK2point mutations have been described―all in regions encoding the pseudokinase domain that regulates the tyrosine kinase activity of JAK2. We present a case of a patient with erythrocytosis and an exon 13 G571S mutation, and discuss the putative role of this mutation in myeloproliferative neoplasms.

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“…Genetic testing in the remaining patients revealed three different previously described missense variants in the JAK2 gene 4,5,32,33 in P16, P17 and P18 (Table 2) with ~50% variant allelic frequency (VAF) (Table 2). The germline origin of JAK2 E846D and JAK2 N1108S was confirmed using DNA from patients' buccal cells; such a sample from P18 with the JAK2 G571S was unavailable.…”

Section: Idiopathic Erythrocytosis-miscellaneousmentioning

confidence: 98%

Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen‐sensing pathway from primary familial and congenital polycythaemia

et al. 2023

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Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular‐genetic analysis of 21 Czech patients with congenital erythrocytosis and assessed the mutual link between chronic erythrocyte overproduction and iron homoeostasis. Causative mutations in erythropoietin receptor (EPOR), hypoxia‐inducible factor 2 alpha (HIF2A) or Von Hippel–Lindau (VHL) genes were detected in nine patients, including a novel p.A421Cfs*4 EPOR and a homozygous intronic c.340+770T>C VHL mutation. The association and possible cooperation of five identified missense germline EPOR or Janus kinase 2 (JAK2) variants with other genetic/non‐genetic factors in erythrocytosis manifestation may involve variants of Piezo‐type mechanosensitive ion channel component 1 (PIEZO1) or Ten‐eleven translocation 2 (TET2), but this requires further research. In two families, hepcidin levels appeared to prevent or promote phenotypic expression of the disease. No major contribution of heterozygous haemochromatosis gene (HFE) mutations to the erythrocytic phenotype or hepcidin levels was observed in our cohort. VHL‐ and HIF2A‐mutant erythrocytosis showed increased erythroferrone and suppressed hepcidin, whereas no overproduction of erythroferrone was detected in other patients regardless of molecular defect, age or therapy. Understanding the interplay between iron metabolism and erythropoiesis in different subgroups of congenital erythrocytosis may improve current treatment options.

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Essential Thrombocythemia Associated With Germline JAK2 G571S Variant and Somatic CALR Type 1 Mutation

Cited by 8 publications

References 14 publications

NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients

NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients

The role of the Exon 13 G571S JAK2 mutation in myeloproliferative neoplasms

Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen‐sensing pathway from primary familial and congenital polycythaemia

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