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.
Keywords: BMPER; DSD; ISD; diaphanospondylodysostosis; ischiospinal dysostosis; skeletal dysplasia.
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.