Molecular Analyses

  1. JAK2V617F
  2. JAK2 Exon 12
  3. MPL/TPO Receptor
  4. CALR
  5. Other MPN mutations
  6. EPO Receptor
  7. O2-sensing pathway genes
  8. THPO/Thrombopoietin

Oxygen sensing pathway genes

The main known causes of primary congenital erythrocytosis are mutations of the erythropoietin receptor. These mutations result in truncations of the receptor and result in a receptor which is activated and signalling in the absence of cytokine stimulus.

Oxygen sensing pathway gene mutations

To date mutations have been described in three genes in the oxygen sensing pathway which lead to elevated erythropoietin levels and congenital secondary erythrocytosis.

Von Hippel-Lindau (VHL) gene mutations

The first and most common mutation was found in an extensive number of individuals in the Chuvash area of Russia. Affected individuals were discovered to be homozygotes for a C598T mutation. Other mutations in the VHL gene have also been associated with erythrocytosis.

Prolyl Hydroxylase Domain 2 (PHD2) gene mutations

The first family with an erythrocytosis due to a PHD2 mutation were all found to be heterozygous for a mutation in the PHD2 gene, C950G. To date at least another 10 mutations have been described.

Hypoxia Inducible Factor2A (HIF2A) gene mutations

The first mutation in HIF2A was described in three generations of a family known to have erythrocytosis. All effected individuals were heterozygous for a mutation of the HIF2A gene, G1609T. At least four further mutations of HIF2A have been discovered in individuals with erythrocytosis.

Hypoxia sensing

Erythrocytosis can be secondary to an increased Epo secretion in relation to an abnormality in the oxygen sensing pathway. See our section Congenital Erythrocytosis. Click here to get a table of the labs exploring oxygen sensing pathways and related genes (details about the labs in the second table).