Thirty-four patients with presumable congenital erythrocytosis due to an unknown underlying disorder were examined for VHL gene mutations and VHL region haplotypes.
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.
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.
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.
Recently, a few mutations in gene for the prolyl hydroxylase domain 2 protein (PHD2) have been reported in cases of congenital erythrocytosisnot associated with tumor formation with the exception of one patient with a recurrent extra-adrenal paraganglioma.
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.
The rs182123615JAK2 variant was described in several contexts including myeloproliferative neoplasms and congenital erythrocytosis and was supposed to be pathogenic.