New pathogenic mechanisms induced by germline erythropoietin receptor mutations in primary erythrocytosis.

ABSTRACT: Primary familial and congenital polycythemia is characterized by erythropoietin hypersensitivity of erythroid progenitors due to germline nonsense or frameshift mutations in the erythropoietin receptor gene. All mutations so far described lead to the truncation of the C-terminal receptor sequence that contains negative regulatory domains. Their removal is presented as sufficient to cause the erythropoietin hypersensitivity phenotype. Here we provide evidence for a new mechanism whereby the presence of novel sequences generated by frameshift mutations is required for the phenotype rather than just extensive truncation resulting from nonsense mutations. We show that the erythropoietin hypersensitivity induced by a new erythropoietin receptor mutant, p.Gln434Profs*11, could not be explained b

SUBMITTER: Pasquier F 

PROVIDER: S-EPMC5865417 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature