Further evidence for causation of ischiospinal dysostosis by a pathogenic variant in BMPER and expansion of the phenotype

Successfully Managed Respiratory Insufficiency in a Patient with a Novel Pathogenic Variant of the BMPER Gene: A Case Report

“…Although DSD and ISD were regarded as different diseases in the past, the recent perspective is that it is reasonable to consider these two diseases as a single disease spectrum of varying severity with overlapping clinical features [7][8][9]. This case report supports the previously proposed hypothesis that DSD, attenuated DSD, and ISD should be considered as a disease spectrum caused by BMPER gene mutations.…”

“…As the number of reported patients is still small, about 30, the factors determining the severity of the disease have not been clearly identified. It was assumed that the type of mutation could affect the severity of the disease by elucidating the mutation type of siblings, considering the characteristics of a disease with an autosomal recessive inheritance pattern due to biallelic mutation [8]. In addition, patient number 23 shared the same allele mutation c.1672C>T as the patient reported in the current study, but had a different disease severity.…”

“…Patients with typical DSD, the fatal phenotype, present with severe respiratory failure during the perinatal period and inevitably undergo invasive ventilation. To date, only approximately 30 patients have been reported to have DSD and ISD [7][8][9].…”

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

“…Only few patients who survived beyond infancy are known and the oldest known patient in the literature is 9 years old. Leading causes of death are respiratory insufficiency and Wilms' tumor (Funari et al, 2010;Ben-Neriah et al, 2011;Zong et al, 2015;Kuchinskaya et al, 2016;Hofstaetter et al, 2018;Legare et al, 2017;Salian et al, 2019;Scottoline et al, 2012, Greenbaum et al, 2019. Ischiospinal dysostosis (ISD) is another congenital, polytopic dysostosis associated with mutations in the BMPER gene, but mostly describes a milder phenotype than DSD and may also be associated with nephroblastomatosis (Kuchinskaya et al, 2016).…”

“…Bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER) is a homologue of Crossveinless (CV-2) in Drosophila melanogaster and part of the chordin family (Helbing et al, 2017). BMPER plays an essential role in organogenesis, osteogenesis, angiogenesis, and endothelialbarrier function (Ben-Neriah et al, 2011;Helbing et al, 2017;Ikeya et al, 2006;Kelley et al, 2009;Salian et al, 2019;Xiao et al, 2018).…”