Expansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process.

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.