Lack of hemizygosity for the insulin-like growth factor I receptor gene in a quantitative study of 33 Silver Russell syndrome probands and their families.

Previous studies have shown that individuals with a deletion of 15q26.1-->qter, which includes the insulin-like growth factor I receptor (IGFIR) gene, may exhibit phenotypic characteristics similar to those individuals with Silver-Russell Syndrome (SRS). Thirty-three SRS probands, with normal karyotypes, and their parents were investigated for the presence of both copies of IGFIR by gene dosage analysis of Southern blot hybridisation. All 33 SRS probands have both copies of IGFIR. Tetranucleotide repeat marker analysis for three locations on 15q also ruled out other deletions in these regions for those markers that were informative. Two important functional regions of IGFIR were also investigated for DNA mutations, using single-stranded conformational polymorphism analysis. No mutations were found in the cysteine-rich region involved in ligand binding (exon 3) or the ATP binding region (exon 16) which could contribute to the SRS phenotype. However, a silent mutation in the third position of one of the codons in the ATP region (3174G-->A, 1013 Glu-->Glu) was found.