title: RUNX2 analysis of Danish cleidocranial dysplasia families.
abstract: Cleidocranial dysplasia (CCD) is an autosomal dominant inherited disease caused by mutations in the Runt gene RUNX2. Screening of 19 Danish CCD families revealed 16 pathogenic mutations (84%) representing 8 missense mutations, 2 nonsense mutations, 4 frame-shift mutations and 2 large deletions in the RUNX2 locus. Eight mutations were novel, two were found twice, and polymorphisms were found in the promoter region and in the conserved polyglutamine/polyalanine repeat. A large duplication downstream of RUNX2 found in one patient suggests a possible regulatory RUNX2 element. The CCD phenotypes and genotypes adhere to the large phenotypic variability reported in previous CCD studies. Identification of large chromosome aberrations in or near the RUNX2 locus in 3 of the 19 cases suggests copy number analyses to be included in future RUNX2 mutation analyses.
authors.affiliation: Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark. lah@sund.ku.dk
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: A K
authors.initials: AK
authors.lastname: Riis
authors.forename: A
authors.initials: A
authors.lastname: Silahtaroglu
authors.forename: H
authors.initials: H
authors.lastname: Hove
authors.forename: E
authors.initials: E
authors.lastname: Lauridsen
authors.forename: H
authors.initials: H
authors.lastname: Eiberg
authors.forename: S
authors.initials: S
authors.lastname: Kreiborg
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002973:Cleidocranial Dysplasia / Q000235:genetics*; D015331:Cohort Studies; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D056915:DNA Copy Number Variations; D003718:Denmark; D005091:Exons; D005260:Female; D023061:Gene Order; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit