title: A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD).
abstract: 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.
authors: Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Ziva
authors: Z
authors: Ben-Neriah
authors: Rachel
authors: R
authors: Michaelson-Cohen
authors: Michal
authors: M
authors: Inbar-Feigenberg
authors: Michael
authors: M
authors: Nadjari
authors: Sharon
authors: S
authors: Zeligson
authors: Avraham
authors: A
authors: Shaag
authors: Shamir
authors: S
authors: Zenvirt
authors: Orly
authors: O
authors: Elpeleg
authors: Ephrat
authors: E
authors: Levy-Lahad
mesh_terms: D018912:Arabs / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005817:Genetic Counseling; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D048208:Nuchal Translucency Measurement; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000235:genetics; D011859:Radiography; D055009:Spondylosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: C476724:BMPER protein, human; D002352:Carrier Proteins