title: A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene.
abstract: In this study, a brother and sister of German origin are described with a possible diagnosis of van Buchem disease, a rare autosomal recessive sclerosing bone dysplasia characterized by a generalized hyperostosis of the skeleton mainly affecting the cranial bones. Clinically, patients suffer from cranial nerve entrapment potentially resulting in facial paresis, hearing disturbances, and visual loss. The radiological picture of van Buchem disease closely resembles sclerosteosis, although in the latter patients, syndactyly, tall stature, and raised intracranial pressure are frequently observed, allowing a differential diagnosis with van Buchem disease. Previous molecular studies demonstrated homozygous loss-of-function mutations in the SOST gene in sclerosteosis patients while a chromosomal rearrangement creating a 52-kb deletion downstream of this gene was found in Dutch patients with van Buchem disease. This deletion most likely suppresses SOST expression. Sclerostin, the SOST gene product, has been shown to play a role in bone metabolism. The two siblings reported here were evaluated at the molecular level by carrying out a mutation analysis of the SOST gene. This resulted in the identification of a novel putative disease-causing splice site mutation (IVS1 + 1 G-->C) homozygously present in both siblings.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Balemans
authors.forename: Erna
authors.initials: E
authors.lastname: Cleiren
authors.forename: Ulrike
authors.initials: U
authors.lastname: Siebers
authors.forename: Jürgen
authors.initials: J
authors.lastname: Horst
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001847:Bone Diseases / Q000235:genetics / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001842:Bone and Bones / Q000473:pathology; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D019066:Facies; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015576:Hyperostosis / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008297:Male; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D022821:RNA Splice Sites / Q000235:genetics; D035781:Siblings
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D022821:RNA Splice Sites; C422903:SOST protein, human; D004247:DNA