EPAS1 p.M535T mutation in a Bulgarian family with congenital erythrocytosis.
OBJECTIVE
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.


CONCLUSIONS
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.


CONCLUSIONS
This is the first description of an entire family with EPAS1 p. M535T mutation expanding our knowledge about the clinical features of the disease.
a Department of Clinical Hematology , Sofiamed University Hospital , Sofia , Bulgaria.
Tzvetan
T
Alaikov
b Laboratory of Clinical Immunology , Alexandrovska University Hospital, Medical University , Sofia , Bulgaria.
Milena
M
Ivanova
a Department of Clinical Hematology , Sofiamed University Hospital , Sofia , Bulgaria.|c Laboratory of Clinical Immunology , Sofiamed University Hospital , Sofia , Bulgaria.
Velizar
V
Shivarov
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002031:Bulgaria; D004911:Erythrocyte Volume; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010375:Pedigree; D011086:Polycythemia / Q000097:blood / Q000151:congenital* / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1
EPAS1; Familial (congenital) erythrocytosis; HIF2A; Mutation