Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families

Am J Med Genet. 1996 Dec 11;66(2):227-34. doi: 10.1002/(SICI)1096-8628(19961211)66:2<227::AID-AJMG20>3.0.CO;2-U.


Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disorder recently shown to be caused by mutations in the heparan sulfate proteoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have used Southern blot analysis and polymerase chain reaction amplification of intra-exonic sequences to identify four new GPC3 mutations and further characterize three previously reported SGBS mutations. De novo GPC3 mutations were identified in 2 families. In general, the mutations were unique deletions ranging from less than 0.1 kb to more than 300 kb in length with no evidence of a mutational hot spot discerned. The lack of correlation between the phenotype of 18 affected males from these 7 families and the location and size of the GPC3 gene mutations suggest that SGBS is caused by a nonfunctional GPC3 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Autoradiography
  • Blotting, Southern
  • Chromosome Deletion*
  • DNA Probes
  • Genotype
  • Heparan Sulfate Proteoglycans
  • Heparitin Sulfate / genetics*
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Proteoglycans / genetics*
  • X Chromosome / genetics


  • DNA Probes
  • Heparan Sulfate Proteoglycans
  • Proteoglycans
  • Heparitin Sulfate