A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene

Al-Sheikh, Maha; Mazurier, Elodie; Gardie, Betty; Casadevall, Nicole; Galactéros, F; Goossens, M; Wajcman, Henri; Préhu, Claude; Ugo, Valérie

doi:10.3324/haematol.12260

Cited by 33 publications

(23 citation statements)

References 21 publications

(16 reference statements)

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“…EpoR -activating mutations have not been observed in erythroleukemias [72, 73], and erythroleukemias are not associated with alterations to chromosome 19 where the EpoR gene is located [72]. EpoR -hyperactivity truncation mutations cause erythrocytosis in humans [74, 75], but not leukemias or tumors [72, 76]. When Gonda et al [72] screened ten human cases of erythroleukemia, no EpoR -gene mutations were found.…”

Section: Epor Mutations/amplification and Epo Overexpressionmentioning

confidence: 99%

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example

et al. 2013

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Testing for the presence of specific cell-surface receptors (such as EGFR or HER2) on tumor cells is an integral part of cancer care in terms of treatment decisions and prognosis. Understanding the strengths and limitations of these tests is important because inaccurate results may occur if procedures designed to prevent false-negative or false-positive outcomes are not employed. This review discusses tests commonly used to identify and characterize cell-surface receptors, such as the erythropoietin receptor (EpoR). First, a summary is provided on the biology of the Epo/EpoR system, describing how EpoR is expressed on erythrocytic progenitors and precursors in the bone marrow where it mediates red blood cell production in response to Epo. Second, studies are described that investigated whether erythropoiesis-stimulating agents could stimulate tumor progression in cancer patients and whether EpoR is expressed and functional on tumor cells or on endothelial cells. The methods used in these studies included immunohistochemistry, Northern blotting, Western blotting, and binding assays. This review summarizes the strengths and limitations of these methods. Critically analyzing data from tests for cell-surface receptors such as EpoR requires understanding the techniques utilized and demonstrating that results are consistent with current knowledge about receptor biology.

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Section: Epor Mutations/amplification and Epo Overexpressionmentioning

confidence: 99%

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example

et al. 2013

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“…In order to avoid extensive sequencing strategies comprising all exons of all genes involved in oxygen sensing and erythropoietin signaling pathways, we validated in this study a protocol in which the most important genes of both pathways are evaluated and, in those two chosen genes, only hotspots exons are sequenced [5, 11–13]. Our protocol consists in sequencing EPOR exon 8, VHL exons 1–3, PHD2 exons 1–5, and HIF2- α exon 12.…”

Section: Resultsmentioning

confidence: 99%

Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis

Dinardo

Santos

Schettert

et al. 2013

Genetics Research International

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Background. Idiopathic erythrocytosis is the term reserved for cases with unexplained origins of abnormally increased hemoglobin after initial investigation. Extensive molecular investigation of genes associated with oxygen sensing and erythropoietin signaling pathways, in those cases, usually involves sequencing all of their exons and it may be time consuming. Aim. To perform a strategy for molecular investigation of patients with idiopathic erythrocytosis regarding oxygen sensing and erythropoietin signaling pathways. Methods. Samples of patients with idiopathic erythrocytosis were evaluated for the EPOR, VHL, PHD2, and HIF-2α genes using bidirectional sequencing of their hotspots. Results. One case was associated with HIF-2α mutation. Sequencing did not identify any pathogenic mutation in 4 of 5 cases studied in any of the studied genes. Three known nonpathogenic polymorphisms were found (VHL p.P25L, rs35460768; HIF-2α p.N636N, rs35606117; HIF-2α p.P579P, rs184760160). Conclusion. Extensive molecular investigation of cases considered as idiopathic erythrocytosis does not frequently change the treatment of the patient. However, we propose a complementary molecular investigation of those cases comprising genes associated with erythrocytosis phenotype to meet both academic and genetic counseling purposes.

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“…Subsequent testing of these kindred demonstrated a heterozygous mutation in EPOR [2]. To date, a further 16 mutations of the EPOR have been described in PFCP [2][3][4][5][6][7][8][9][10][11][12][13][14] The erythrocytosis in PFCP is due to increased sensitivity of erythroid progenitors to erythropoietin (EPO) [1][2][3][4][5][6][9][10][11][12] and is associated with low serum erythropoietin levels [1,2,7,8,14,15]. Patients with PFCP have normal haemoglobin-oxygen dissociation curves [15], do not have splenomegaly and there is no risk of transformation to acute leukaemia [16].…”

Section: Introductionmentioning

confidence: 99%

“…Primary familial and congenital polycythemia (PFCP) is a rare cause of inherited erythrocytosis due to mutations in the erythropoietin receptor gene (EPOR) [1][2][3][4][5][6][7][8][9][10][11][12][13][14] PFCP was first described in a family of Finnish decent, in which erythrocytosis was inherited in an autosomal dominant fashion [1]. Subsequent testing of these kindred demonstrated a heterozygous mutation in EPOR [2].…”

Section: Introductionmentioning

confidence: 99%

A novel mutation of the erythropoietin receptor gene associated with primary familial and congenital polycythaemia

et al. 2011

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Primary familial and congenital polycythaemia (PFCP) is a rare form of inherited erythrocytosis caused by heterozygous mutations in the erythropoietin receptor gene (EPOR). We present a novel mutation in the EPOR in a 15-year-old male who was referred to our clinic for investigation of a persistently elevated haemoglobin level. A significant family history of unexplained erythrocytosis spanning four generations of the patient's family was established. The family history was also significant for an apparent increased rate of cerebrovascular disease in individuals with erythrocytosis. The mutation detected in our patient resides in exon 8 of EPOR, similar to all other EPOR mutations responsible for PFCP. These mutations result in truncation of the cytoplasmic domain of the receptor and impair down-regulation of signalling via the erythropoietin receptor (EPOR). Clinical manifestations in published cases have varied widely and there is a paucity of firm recommendations regarding the management of affected patients. Given the strong family history of complications attributable to erythrocytosis we have recommended venesection with a haematocrit target of ≤0.45 for our patient.

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A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene

Cited by 33 publications

References 21 publications

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example

Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis

A novel mutation of the erythropoietin receptor gene associated with primary familial and congenital polycythaemia

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