title: A novel GLI3 mutation affecting the zinc finger domain leads to preaxial-postaxial polydactyly-syndactyly complex.
abstract: BACKGROUND
  Polydactyly is a highly common congenital limb defect. Extra digits may appear as an isolated anomaly or as a part of a syndrome. Mutations in GLI3 have been shown to cause Greig cephalopolysyndactyly, Pallister-Hall syndrome and non-syndromic polydactyly. Genotype-phenotype correlation studies of GLI3 mutations suggest a model by which mutations in the zinc-finger domain (ZFD) of GLI3 likely lead to syndromic polydactyly. Here we describe a rare case of autosomal dominant heterozygous missense mutation in the ZFD of GLI3 leading to a variable polydactyly-syndactyly complex.
  
  
  METHODS
  A large Jewish Moroccan family presented with apparently autosomal dominant heredity of bilateral thumb polydactyly in hands and feet combined with post-axial polydactyly type B or type A. Syndactyly was evident in most patients' hands and feet. Apart from head circumference beyond 90th percentile in some of the affected individuals, none had craniofacial dysmorphism. A novel GLI3 c.1802A > G (p.His601Arg) mutation was found in all affected individuals.
  
  
  CONCLUSIONS
  We demonstrate that a mutation in the ZFD domain of GLI3 leads to phenotypic variability, including an isolated limb phenotype. Thus, the variability in phenotypes caused by mutations in this master developmental regulator is more profound than has been previously suggested.
authors.forename: Michael
authors.initials: M
authors.lastname: Volodarsky
authors.forename: Yshaia
authors.initials: Y
authors.lastname: Langer
authors.affiliation: The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva 84105, Israel. obirk@bgu.ac.il.
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D001120:Arginine / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006639:Histidine / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D009018:Morocco; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017689:Polydactyly / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D017434:Protein Structure, Tertiary; D013576:Syndactyly / Q000150:complications* / Q000235:genetics* / Q000473:pathology; 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; D006639:Histidine; D001120:Arginine