heparitin-sulfate and Chromosome-Deletion

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.

Topics: Abnormalities, Multiple; Autoradiography; Blotting, Southern; Chromosome Deletion; DNA Probes; Genotype; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Male; Mutation; Pedigree; Phenotype; Polymerase Chain Reaction; Proteoglycans; X Chromosome

Topics: Abnormalities, Multiple; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, 4-5; Dermatoglyphics; Glycosaminoglycans; Heparitin Sulfate; Humans; Infant, Newborn; Male