title: Diaphanospondylodysostosis: six new cases and exclusion of the candidate genes, PAX1 and MEOX1.
abstract: We report on six cases from four families with the newly described skeletal disorder diaphanospondylodysostosis (DSD). The characteristic radiographic findings included abnormal ossification of vertebral bodies, posterior rib gaps, missing ribs, and a downward tilt of the pubic rami, but normal long bones. The typical facial features of DSD cases were ocular hypertelorism, a short nose, depressed nasal bridge, and low set ears. Other distinctive findings included a short neck with bell-shaped thorax, and nephroblastomatosis. A history of consanguinity and affected siblings with unaffected parents supports autosomal recessive inheritance. Skeletal histology showed incomplete ossification of the ribs, vertebral bodies, and sacrum as well as incomplete formation of intervertebral discs. The posterior ribs were comprised of bone with intervening cartilage interrupted by dense fibrous tissue and skeletal muscle fascicles. These findings suggest abnormal development and differentiation of the paraxial mesoderm. Because of phenotypic similarities of DSD to Pax1 and Meox1 deficient mice, we sequenced genomic DNA from three unrelated DSD cases. No mutations were identified in the PAX1 and MEOX1 exons or flanking intronic sequences, excluding them as likely causative genes.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Nithiwat
authors.initials: N
authors.lastname: Vatanavicharn
authors.forename: John M
authors.initials: JM
authors.lastname: Graham
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Curry
authors.forename: Samuel
authors.initials: S
authors.lastname: Pepkowitz
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Lachman
authors.forename: David L
authors.initials: DL
authors.lastname: Rimoin
authors.forename: William R
authors.initials: WR
authors.lastname: Wilcox
mesh_terms: D000369:Aged, 80 and over; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005260:Female; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051761:Paired Box Transcription Factors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013169:Spondylolysis / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; C525671:MEOX1 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C070835:PAX1 transcription factor; D004247:DNA