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

Abstract

BackgroundDiaphanospondylodysostosis (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.MethodsWe report on the case of a 22‐month‐old patient with DSD where trio‐exome sequencing was performed.ResultsGenetic 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.ConclusionsOur findings expand the genotypic and phenotypic spectrum of BMPER variants leading to DSD.

Diaphanospondylodysostosis: Full Case Report with Novel Pathogenic BMPER Mutation

“…First described in 1999, its incidence is unknown, with only isolated reports in the medical literature. [1][2][3][4][5] The diagnosis is clinical and radiological, although diagnostic confirmation must be made by genetic study of the BMPER gene, which is mutated in all patients affected by this entity. From a clinical point of view, these patients are characterized by defects of costal ossification and absence of ribs, which determines the presence of a narrow thorax that conditions their ventilatory mechanics.…”