title: BMPER variants associated with a novel, attenuated subtype of diaphanospondylodysostosis.
abstract: Diaphanospondylodysostosis (DSD), caused by loss of bone morphogenetic protein-binding endothelial regulator (BMPER), has been considered a lethal skeletal dysplasia characterized by severe deficiency of vertebral body and sacral ossification, reduced rib number and cystic kidneys. In this study, however, we have demonstrated that variants in BMPER may cause a milder disorder, without renal anomalies, that is compatible with long-term survival. Four siblings, three males and one female, presented with severe congenital scoliosis associated with rib and vertebral malformations as well as strikingly delayed ossification of the pedicles. The female was stillborn from an unrelated cause. Stabilization of the scoliosis with expandable titanium rods was successful in the three boys, all of whom have short stature. An autosomal recessive mode of inheritance was hypothesized. Single nucleotide polymorphism microarray analysis was performed for three of the siblings to identify autosomal genes with shared allele patterns, suggesting possible linkage. Exome sequencing of one sibling was then performed. Rare variants were identified in 347 genes with shared alleles. Only one of these genes had bi-allelic variants in a gene strongly expressed in paraxial mesenchyme: BMPER, which is the cause of DSD, an autosomal recessive disorder. The disorder described herein could represent an attenuated form of DSD or could be designated a separate entity such as spondylopedicular dysplasia.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.|Child and Family Research Institute, Vancouver, Canada.
authors.forename: Zheyuan
authors.initials: Z
authors.lastname: Zong
authors.affiliation: Tees IP, Vancouver, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Tees
authors.affiliation: Child and Family Research Institute, Vancouver, Canada.|Department of Surgery, University of British Columbia, Vancouver, Canada.
authors.forename: Firoz
authors.initials: F
authors.lastname: Miyanji
authors.affiliation: Department of Pathology, University of British Columbia, Vancouver, Canada.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Fauth
authors.affiliation: Child and Family Research Institute, Vancouver, Canada.|Department of Surgery, University of British Columbia, Vancouver, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Reilly
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.|Child and Family Research Institute, Vancouver, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez
authors.affiliation: Child and Family Research Institute, Vancouver, Canada.|Department of Surgery, University of British Columbia, Vancouver, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tredwell
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Yigal
authors.initials: Y
authors.lastname: Paul Goldberg
authors.affiliation: Genome Sciences Centre, Vancouver, Canada.
authors.forename: Allen
authors.initials: A
authors.lastname: Delaney
authors.affiliation: Child and Family Research Institute, Vancouver, Canada.|Department of Pathology, University of British Columbia, Vancouver, Canada.
authors.forename: Patrice
authors.initials: P
authors.lastname: Eydoux
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.|Child and Family Research Institute, Vancouver, Canada.
authors.forename: Margot
authors.initials: M
authors.lastname: Van Allen
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.|Child and Family Research Institute, Vancouver, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Lehman
mesh_terms: D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D004413:Dysostoses / Q000235:genetics* / Q000473:pathology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012272:Ribs / Q000002:abnormalities* / Q000473:pathology; D013131:Spine / Q000002:abnormalities* / Q000473:pathology
chemical_list: C476724:BMPER protein, human; D002352:Carrier Proteins