title: An N-terminal G11A mutation in HOXD13 causes synpolydactyly and interferes with Gli3R function during limb pre-patterning.
abstract: Synpolydactyly (SPD) is a distal limb anomaly characterized by incomplete digit separation and the presence of supernumerary digits in the syndactylous web. This phenotype has been associated with mutations in the homeodomain or polyalanine tract of the HOXD13 gene. We identified a novel mutation (G11A) in HOXD13 that is located outside the previously known domains and affects the intracellular half life of the protein. Misexpression of HOXD13(G11A) in the developing chick limb phenocopied the human SPD phenotype. Finally, we demonstrated through in vitro studies that this mutation has a destabilizing effect on GLI3R uncovering an unappreciated mechanism by which HOXD13 determines the patterning of the limb.
authors.affiliation: Laboratory of Skeletal Development and Joint Disorders, University of Leuven, Herestraat 49, O&N1 Box 813, 3000 Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brison
authors.forename: Philippe
authors.initials: P
authors.lastname: Debeer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fantini
authors.forename: Christine
authors.initials: C
authors.lastname: Oley
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Zappavigna
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
authors.forename: Przemko
authors.initials: P
authors.lastname: Tylzanowski
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019556:COS Cells; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010641:Phenotype; D013576:Syndactyly / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000074290:Zinc Finger Protein Gli3
chemical_list: C065683:GLI3 protein, human; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3