Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations

Am J Med Genet A. 2003 Jul 1;120A(1):49-58. doi: 10.1002/ajmg.a.20018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Craniofacial Abnormalities / diagnostic imaging
  • Craniofacial Abnormalities / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Facies
  • Family Health
  • Female
  • Genes, Dominant
  • Genetic Markers
  • Heterozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kruppel-Like Transcription Factors
  • Limb Deformities, Congenital / diagnostic imaging
  • Limb Deformities, Congenital / genetics
  • Male
  • Mutation*
  • Mutation, Missense
  • Nerve Tissue Proteins*
  • Pedigree
  • Penetrance
  • Phenotype
  • Polydactyly / diagnostic imaging
  • Polydactyly / genetics
  • Polymorphism, Single-Stranded Conformational
  • Radiography
  • Syndactyly / diagnostic imaging
  • Syndactyly / genetics
  • Syndrome
  • Transcription Factors / genetics*
  • Zinc Finger Protein Gli3

Substances

  • DNA-Binding Proteins
  • GLI3 protein, human
  • Genetic Markers
  • Gli3 protein, mouse
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Transcription Factors
  • Zinc Finger Protein Gli3