Open AccessExpansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process
Author(s) -
Braun Frederik,
Gangfuß Andrea,
Stöbe Petra,
Haack Tobias B.,
Schweiger Bernd,
Roos Andreas,
Schara Ulrike
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1767
Subject(s) - exome sequencing , genetics , biology , bone morphogenetic protein , nonsense mutation , nonsense mediated decay , mutation , gene , missense mutation , rna , rna splicing
Background Diaphanospondylodysostosis (DSD) is a rare congenital, lethal skeletal disorder caused by recessively inherited mutations in the BMPER gene, which encodes the bone morphogenetic protein‐binding endothelial cell precursor‐derived regulator. The most prominent features of DSD are missing ossification of the axial skeleton, rib abnormalities and thoracic hypoplasia/insufficiency, as well as intralobar nephrogenic rests within the kidneys. Methods We report on the case of a 22‐month‐old patient with DSD where trio‐exome sequencing was performed. Results Genetic testing revealed a homozygous nonsense variant c.1577G>A (p.Trp526*) in the BMPER gene, leading to a premature stop in protein translation. Both parents are asymptomatic carriers for the BMPER variant, which has not been described in the literature before. Conclusions Our findings expand the genotypic and phenotypic spectrum of BMPER variants leading to DSD.