Homozygous missense and nonsense mutations in BMPR1B cause acromesomelic chondrodysplasia-type Grebe.

ABSTRACT: Acromesomelic chondrodysplasias (ACDs) are characterized by disproportionate shortening of the appendicular skeleton, predominantly affecting the middle (forearms and forelegs) and distal segments (hands and feet). Here, we present two consanguineous families with missense (c.157T>C, p.(C53R)) or nonsense (c.657G>A, p.(W219*)) mutations in BMPR1B. Homozygous affected individuals show clinical and radiographic findings consistent with ACD-type Grebe. Functional analysis of the missense mutation C53R revealed that the mutated receptor was partially located at the cell membrane. In contrast to the wild-type receptor, C53R mutation hindered the activation of the receptor by its ligand GDF5, as shown by reporter gene assay. Further, overexpression of the C53R mutation in an in vitro chondrogene

SUBMITTER: Graul-Neumann LM 

PROVIDER: S-EPMC4023204 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature