How to Cite this Article: Ben-Neriah Z, Michaelson-Cohen R, Inbar-Feigenberg M, Nadjari M, Zeligson S, Shaag A, Zenvirt S, Elpeleg O, Levy-Lahad E. 2011. A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD). Am J Med Genet Part A 155: 2801–2806.
Article first published online: 11 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 11, pages 2801–2806, November 2011
How to Cite
Ben-Neriah, Z., Michaelson-Cohen, R., Inbar-Feigenberg, M., Nadjari, M., Zeligson, S., Shaag, A., Zenvirt, S., Elpeleg, O. and Levy-Lahad, E. (2011), A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD). Am. J. Med. Genet., 155: 2801–2806. doi: 10.1002/ajmg.a.34240
Ziva Ben-Neriah and Rachel Michaelson-Cohen contributed equally to this work.
- Issue published online: 20 OCT 2011
- Article first published online: 11 OCT 2011
- Manuscript Accepted: 7 JUL 2011
- Manuscript Received: 12 MAR 2011
- homozygosity mapping;
- BMPER gene;
- skeletal dysplasia
Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab-Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be <1:123. Our findings confirm loss of BMPER function as a cause of axial versus appendicular skeletal defects, and suggest that less deleterious mutations may be involved in milder axial skeleton abnormalities. © 2011 Wiley Periodicals, Inc.