title: De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models.
abstract: Acrocallosal syndrome (ACS) is characterised by postaxial polydactyly, hallux duplication, macrocephaly, and absence of the corpus callosum, usually with severe developmental delay. The condition overlaps with Greig cephalopolysyndactyly syndrome (GCPS), an autosomal dominant disorder that results from mutations in the GLI3 gene. Here we report a child with agenesis of the corpus callosum and severe retardation, both cardinal features of ACS and rare in GCPS, who has a mutation in GLI3. Since others have excluded GLI3 in ACS, we suggest that ACS may represent a heterogeneous group of disorders that, in some cases, may result from a mutation in GLI3 and represent a severe, allelic form of GCPS. The finding is important for counselling families with suspected ACS.
authors.affiliation: Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK.
authors.forename: E
authors.initials: E
authors.lastname: Elson
authors.forename: R
authors.initials: R
authors.lastname: Perveen
authors.forename: D
authors.initials: D
authors.lastname: Donnai
authors.forename: S
authors.initials: S
authors.lastname: Wall
authors.forename: G C M
authors.initials: GC
authors.lastname: Black
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D061085:Agenesis of Corpus Callosum; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D008607:Intellectual Disability / Q000473:pathology*; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D010641:Phenotype; D017689:Polydactyly / Q000473:pathology*; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3
chemical_list: D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3; D004247:DNA