Erythrocytosis, Familial, 3
A number sign (#) is used with this entry because familial erythrocytosis-3 is caused by heterozygous mutation in the EGLN1 gene (606425) on chromosome 1q42.
For a general phenotypic description and a discussion of genetic heterogeneity of familial erythrocytosis, see ECYT1 (133100).
Clinical FeaturesPercy et al. (2006) reported a family in which a father, son, and daughter had erythrocytosis characterized by increased serum hemoglobin and hematocrit. Serum levels of erythropoietin (EPO; 133170) were inappropriately normal, suggesting dysregulation of the EPO axis.
Ladroue et al. (2008) reported a man with erythrocytosis and recurrent paraaortic paraganglioma. He had hypertension associated with the tumor. There was no family history of either disorder.
Molecular GeneticsIn all 3 affected members of a family with erythrocytosis, Percy et al. (2006) identified a heterozygous mutation in the EGLN1 gene (606425.0001).
Percy et al. (2007) identified a second heterozygous mutation in the EGLN1 gene (606425.0002) in a patient with modest erythrocytosis and inappropriately normal EPO levels.
In a man with erythrocytosis and recurrent paraaortic paraganglioma, Ladroue et al. (2008) identified a heterozygous mutation in the EGLN1 gene (H374R; 605425.0003). The authors noted that hereditary paraganglioma syndromes (see, e.g., PGL1; 168000) can be caused by mutations in genes encoding succinate dehydrogenase (see, e.g., SDHD; 602690), which result in accumulation of succinate and inhibition of PHD function with overexpression of hypoxia inducible factor (see, e.g., HIF1A; 603348). Examination of tumor tissue showed the H374R mutation and loss-of-heterozygosity for the wildtype EGLN1 allele. The findings suggested that EGLN1 may also act as a tumor-suppressor gene. Ladroue et al. (2008) suggested that alteration of the EGLN1/HIF pathway could contribute to the growth of a paraganglioma. No germline mutations were identified in the VHL gene (608537), which is involved in the same pathway.