title: Tibial hemimelia associated with GLI3 truncation.
abstract: Tibial hemimelia is a rare, debilitating and often sporadic congenital deficiency. In syndromic cases, mutations of a Sonic hedgehog (SHH) enhancer have been identified. Here we describe an ~5 kb deletion within the SHH repressor GLI3 in two patients with bilateral tibial hemimelia. This deletion results in a truncated GLI3 protein that lacks a DNA-binding domain and cannot repress hedgehog signaling. These findings strengthen the concept that tibial hemimelia arises because of failure to restrict SHH activity to the posterior aspect of the limb bud.
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Deimling
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Sotiropoulos
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lau
authors.affiliation: Division of Orthopaedic Surgery, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Chaudhry
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Kendra
authors.initials: K
authors.lastname: Sturgeon
authors.affiliation: Division of Orthopaedic Surgery, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Kelley
authors.affiliation: Division of Orthopaedic Surgery, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Unni
authors.initials: U
authors.lastname: Narayanan
authors.affiliation: Division of Orthopaedic Surgery, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Howard
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.|Division of Orthopaedic Surgery, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sevan
authors.initials: S
authors.lastname: Hopyan
mesh_terms: D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D004480:Ectromelia / Q000175:diagnosis* / Q000235:genetics*; D005091:Exons; D056726:Genetic Association Studies; D006801:Humans; D054643:INDEL Mutation; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012863:Skeleton / Q000000981:diagnostic imaging / Q000473:pathology; D013977:Tibia / Q000002:abnormalities*; D000074290:Zinc Finger Protein Gli3
chemical_list: C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3