Constitutionally short stature: analysis of the insulin-like growth factor-I gene and the human growth hormone gene cluster.

It has been suggested that modifications of the IGF-I gene might be responsible for constitutionally short stature (CSS). To assess this possibility, and to examine the possible role of the hGH gene cluster in CSS, we used Southern blotting and restriction fragment length polymorphism (RFLP) linkage analysis to study 57 children with CSS, including 17 children from 10 families with CSS. We studied as control populations 50 children and 25 adults of normal height, including three families, and 60 children with isolated growth hormone deficiency. No gross structural abnormalities of the IGF-I gene or the hGH gene cluster were found in any of the subjects. The allelic frequencies for each of two distinct RFLP associated with the IGF-I gene (EcoRV and HindIII/PvuII) and for each of five distinct RFLP associated with the hGH gene cluster [BglII(A), BglII(B), MspI(A), MspI(B), and HincII] were the same in the CSS, isolated growth hormone deficiency, and normal populations, and the RFLP haplotypes for both the IGF-I gene and the hGH gene cluster also appeared with the same frequency in all three populations. Analysis of the families that contained heterozygotes for the HindIII/PvuII and/or EcoRV IGF-I RFLP excluded a linkage of the IGF-I gene to CSS in these families. Assuming that the inheritance is dominant, the lod score at 1% recombination was -2.2, whereas assuming a recessive inheritance, the lod score at 1% recombination was -1.93.(ABSTRACT TRUNCATED AT 250 WORDS)