We analyzed mutations of the GPC3gene in seven males with typical manifestations of Simpson-Golabi-Behmel syndrome (SGBS). Genomic DNA was PCR amplified for its all eight exons and exon-intron boundaries using designed set of primers, and PCR products were directly sequenced. All seven males studied had mutations: One patient had a large deletion spanning introns 6 and 7, four each had a C --> T base substitution resulting in a stop codon formation in exons 2, 3, and 4, one had a single-base insertion in exon 2, and the other had a six-base deletion and a three-base insertion in exon 3; all resulting in loss-of-function of the glypican-3 protein. These results, together with previous studies of GPC3 mutations, indicate that there is no hot spot for GPC3 mutations or deletions in the patients with the syndrome. Also, no correlation has been noted between the location and nature of mutations and the phenotype of the patients studied, as is the case of the present study.
(c) 2007 Wiley-Liss, Inc.