[Pathology of the growth and abnormalities of IGF genes]

Insulin like growth factor I (IGF I) and IGF II have both metabolic and growth promoting properties, both display endocrine and autocrine-paracrine effects. In growth stature disorders without GH deficiency (constitutionally short stature = CSS, pygmy) no IGF I gene deletion was detectable by Southern blotting. In CSS the incidence of RFLP for Hind III located near exon 5 was similar to that in the control population, the incidence of the polymorphic (13 kb) EcoRV (located near exon 1) was significantly lower. Cosegregation analysis of these RFLP in families of CSS were uniformative for IGF I gene, but family linkage studies by others demonstrated co-segragation of the IGF I gene region and hypochondroplasia. In pygmy, DNA amplification around exon 1 and direct sequencing revealed polymorphic sites. One of them is located in the consensus sequence upstream from the translational start site in Eucaryotic mRNA. IGF II RNA messenger hyperexpression was noted in many human tumours with genomic abnormalities: IGF II gene hypomethylation, and loss of allele.