title: Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis.
abstract: Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.
authors.affiliation: Institute for Medical Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany. eva.klopocki@charite.de
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Silke
authors.initials: S
authors.lastname: Lohan
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Randi
authors.initials: R
authors.lastname: Koll
authors.forename: Anja
authors.initials: A
authors.lastname: Brehm
authors.forename: Petra
authors.initials: P
authors.lastname: Seemann
authors.forename: Katarina
authors.initials: K
authors.lastname: Dathe
authors.forename: Sigmar
authors.initials: S
authors.lastname: Stricker
authors.forename: Jochen
authors.initials: J
authors.lastname: Hecht
authors.forename: Kristin
authors.initials: K
authors.lastname: Bosse
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Garaci
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Mahim
authors.initials: M
authors.lastname: Jain
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
authors.forename: Vivian C W
authors.initials: VC
authors.lastname: Ng
authors.forename: Wilson
authors.initials: W
authors.lastname: Chan
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
mesh_terms: D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D003398:Craniosynostoses / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D005385:Fingers / Q000254:growth & development; D020440:Gene Duplication; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D056426:Genetic Loci; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D012886:Skull / Q000254:growth & development; D013576:Syndactyly / Q000235:genetics*
chemical_list: D053823:Hedgehog Proteins; C509246:IHH protein, human; C514061:ihh protein, mouse