Recently, a missense mutation [c.950C>G (p.Pro317Arg)] in the prolyl hydroxylase domain protein 2 (PHD2) gene, whose encoded protein has HIF-1alpha as a substrate, provided evidence of the PHD2 role in a case of familial erythrocytosis.
The variants display differential effects on catalytic rate and substrate binding, implying that partial inhibition or selective inhibition with regard to HIFalpha isoforms of PHD2 could result in the phenotype displayed by patients with familial erythrocytosis.
A recent report of familial erythrocytosis now implicates a different protein, Prolyl Hydroxylase Domain protein 2 (PHD2), which is an enzyme that hydroxylates HIF.
We show that this mutation in PHD2 results in a marked decrease in enzyme activity and is associated with familial erythrocytosis, identifying a previously unrecognized cause of this condition.
The rs182123615JAK2 variant was described in several contexts including myeloproliferative neoplasms and congenital erythrocytosis and was supposed to be pathogenic.
We assessed 41 PCCs/PGLs for mutations in EPAS1 and herein describe the clinical, molecular and genetic characteristics of the 7 patients found to carry somatic EPAS1 mutations; 4 presented with multiple PGLs (3 of them also had congenital erythrocytosis), whereas 3 were single sporadic PCC/PGL cases.
We describe here the identification of two cases of familial erythrocytosis associated with heterozygous HIF2A missense mutations, namely Ile533Val and Gly537Arg.
These results suggest a role for Stat5 in regulation of Epo-mediated cell growth and implicate altered kinetics of Epo-induced Jak2 and Stat5 activation in the pathogenesis of familial erythrocytosis associated with this naturally occurring EpoR gene mutation.
We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5.
These results suggest a role for Stat5 in regulation of Epo-mediated cell growth and implicate altered kinetics of Epo-induced Jak2 and Stat5 activation in the pathogenesis of familial erythrocytosis associated with this naturally occurring EpoR gene mutation.
These results suggest a role for Stat5 in regulation of Epo-mediated cell growth and implicate altered kinetics of Epo-induced Jak2 and Stat5 activation in the pathogenesis of familial erythrocytosis associated with this naturally occurring EpoR gene mutation.
We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5.
We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5.
Two other hypoxia-inducible factor alpha (HIFA) subunits, HIF1A and HIF3A, have not yet been associated with medical history of FE, but have potential role in the development of erythrocytosis.
Recently, a missense mutation [c.950C>G (p.Pro317Arg)] in the prolyl hydroxylase domain protein 2 (PHD2) gene, whose encoded protein has HIF-1alpha as a substrate, provided evidence of the PHD2 role in a case of familial erythrocytosis.