Objectives: In the last decade the identification of germline mutations in several genes such as EPOR, VHL, EGLN1, and EPAS1, helped the definition of several different subtypes of familial (congenital) erythrocytosis. Being rare disorders these entities often remain unrecognized or misdiagnosed, which necessitates the extensive reporting of newly identified cases.
Methods: We applied a genetic approach including whole exome sequencing and Sanger sequencing for the identification of the causative germline mutation in a Bulgarian family with congential erythrocytosis.
Results: We identified EPAS1 (HIF2A) p. M535T heterozygous mutation carried by four members of the family over three generations. We provide also an extensive description of the clinical features of the affected family members.
Discussion: EPAS1 p.M535T appears to be found in different populations as a causative variation in familial erythrocytosis. Our findings support the notion that the affected patients present with variable clinical features and disease course. Furthermore, close clinical follow-up with phlebotomies on demand and regular intake of low doses of anticoagulants seem to prevent from serious complications such as thrombembolic events and pulmonary hypertension.
Conclusion: This is the first description of an entire family with EPAS1 p. M535T mutation expanding our knowledge about the clinical features of the disease.
Keywords: EPAS1; Familial (congenital) erythrocytosis; HIF2A; Mutation.