Department of Neuropediatrics, Essen University Hospital, Essen, Germany.
Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany.
Mol Genet Genomic Med. 2021 Dec;9(12):e1767. doi: 10.1002/mgg3.1767. Epub 2021 Jul 20.
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.
We report on the case of a 22-month-old patient with DSD where trio-exome sequencing was performed.
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.
Our findings expand the genotypic and phenotypic spectrum of BMPER variants leading to DSD.
Diaphanospondylodysostosis（DSD）是一种罕见的先天性致死性骨骼疾病，由 BMPER 基因的隐性遗传突变引起，该基因编码骨形态发生蛋白结合内皮细胞前体衍生的调节剂。DSD 的最突出特征是轴骨骼的骨化缺失、肋骨异常和胸壁发育不全/不足，以及肾脏内的叶内肾源性残余物。
我们报告了一例 22 个月大的 DSD 患者，对其进行了 trio-exome 测序。
基因检测显示 BMPER 基因中存在纯合无义变异 c.1577G>A（p.Trp526*），导致蛋白质翻译提前终止。父母均为 BMPER 变异的无症状携带者，该变异以前未在文献中描述过。
我们的发现扩展了导致 DSD 的 BMPER 变异的基因型和表型谱。
