Screening for mutations in the promoter and the coding region of the IGFBP1 and IGFBP3 genes in Silver-Russell syndrome patients

In the present study we sought to identify genetic variation in genes for i nsulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12 -13 which th rough alteration of protein function or level of expression mi ght contribute to the manifestation of Silver-Russell syndrome. Genomic DNA samples from 49 Silver-Russell syndrome (SRS) patients and from unaffected controls were investigated by single-strand conformation analysis. Overlap ping polymerase chain reaction fragments covered the whole coding sequences as well as the 5' untranslated region of the IGFBP1 and IGFBP3 genes. We d etected 3 new polymorphisms in the transcribed sequence of IGFBP1, one amin o acid polymorphism in exon 1 of IGFBP3 and four variants in its promotor r egion and in intron 1. They all occurred in similar frequencies in SRS pati ents and in controls. Thus, paternally inherited mutations in the promoter and coding regions of IGFBP1 and IGFBP3 genes play neither a major nor a mi nor role in the etiology of SRS, The newly detected polymorphisms in the co ding region are powerful tools for analysis of imprinting status and for de tection of possible changes in the imprinting patterns of the two genes.