title: Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations.
abstract: Greig cephalopolysyndactyly (GCPS) (OMIM 175700) is an autosomal dominant disorder characterized by a distinct combination of craniofacial, hand and foot malformations. In this report, clinical and radiological findings of 12 patients with GCPS derived from 4 independent families and 3 sporadic cases with documented GLI3 mutations are presented with particular emphasis on inter- and intrafamilial variability. In a particularly instructive family in which 9 members of 4 generations could be studied clinically and molecularly, a missense mutation (R625W) is transmitted and shows a partially penetrant pattern. In a branch of the family, the GCPS phenotype skips a generation via a normal female carrier without clinical signs providing evidence that GCPS does not always manifest full penetrance as generally supposed.
authors.affiliation: Centre for Human Genetics, Herestraat 49, B-3000 Leuven, Belgium. philippe.debeer@med.kuleuven.ac.be
authors.forename: Philippe
authors.initials: P
authors.lastname: Debeer
authors.forename: H
authors.initials: H
authors.lastname: Peeters
authors.forename: S
authors.initials: S
authors.lastname: Driess
authors.forename: L
authors.initials: L
authors.lastname: De Smet
authors.forename: K
authors.initials: K
authors.lastname: Freese
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: D
authors.initials: D
authors.lastname: Bornholdt
authors.forename: K
authors.initials: K
authors.lastname: Devriendt
authors.forename: K-H
authors.initials: KH
authors.lastname: Grzeschik
authors.forename: J-P
authors.initials: JP
authors.lastname: Fryns
authors.forename: M
authors.initials: M
authors.lastname: Kalff-Suske
mesh_terms: D000483:Alleles; D019465:Craniofacial Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D019066:Facies; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051741:Kruppel-Like Transcription Factors; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D017689:Polydactyly / Q000000981:diagnostic imaging / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011859:Radiography; D013576:Syndactyly / Q000000981:diagnostic imaging / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000074290:Zinc Finger Protein Gli3
chemical_list: D004268:DNA-Binding Proteins; C065683:GLI3 protein, human; D005819:Genetic Markers; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3