Insulin-like growth factor 1 receptor (IGF1R) is a receptor that binds insulin-like growth factor with a high affinity and plays a critical role in transformation events. Cleavage of the IGF1R precursor generates alpha and beta subunits. It is highly overexpressed in many malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Mutations in the IGF1R gene results in IGF1 resistance which may underlie some cases of prenatal and postnatal growth failure.
The IGFBP3 gene (insulin-like growth factor binding protein 3) is a member of the insulin-like growth factor binding protein (IGFBP) family. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. The IGFs family comprise of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of growth hormone.
The IGF1R gene (21 exons), spans ~315 kb of genomic DNA and is located on chromosome 15q26.3, ~99 Mb from the q-telomere. This probemix contains one probe per exon for exons 3 to 20, two probes for exons 1 and 2 and three probes for exon 21. The IGFBP3 gene (5 exons) spans ~9 kb and is located on chromosome 7p12.3, ~46 Mb from the p-telomere. The IGFALS gene (2 exons) spans ~3.3 kb of genomic DNA and is located on 16p13.3, ~1.8 Mb from the p-telomere. One probe for each exon of the IGFBP3 and IGFALS genes are included. In addition, a second probe for IGFBP3 exon 5 and for IGFALS exon 2 has been added. In addition, 8 reference probes are included in this probemix, detecting 8 different autosomal chromosomal locations.
This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned genes in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.