SIMPSON-GOLABI-BEHMEL SYNDROME - GENOTYPE PHENOTYPE ANALYSIS OF 18 AFFECTED MALES FROM 7 UNRELATED FAMILIES/

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disord er recently shown to be caused by mutations in the heparan sulfate pro teoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have use d Southern blot analysis and polymerase chain reaction amplification o f intra-exonic sequences to identify four new GPC3 mutations and furth er characterize three previously reported SG;BS mutations. De novo GPC 3 mutations were identified in 2 families. In general, the mutations w ere 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 la ck of correlation between the phenotype of 18 affected males from thes e 7 families and the location and size of the GPC3 gene mutations sugg est that SGBS is caused by a nonfunctional GPC3 protein. (C) 1996 Wile y-Liss, Inc.