Serum GH binding protein activities identifies the heterozygous carriers for Laron type dwarfism

Measurement of GH-binding protein activity and IGF-I was carried out in the sera of 13 patients with Laron type dwarfism, a syndrome caused by a lack of GH receptors which leads to impairment of IGF-I generation, and those of 16 of their close relatives. GH binding protein activity was measured by incubating 125I-hGH with 100 microliters serum in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 125I-hGH binding protein complexes from free 125I-hGH by gel filtration. The results are expressed as percent specific binding relative to an adult reference serum. IGF-I was determined by RIA after acid extraction on octadecylsilane silica columns. All Laron type dwarfism patients had no, or only negligible GH binding protein activity, which supports the evidence that serum GH binding protein corresponds to the extracellular domain of the membranal GH receptor. Eight of the 16 relatives had serum GH binding protein activity more than 2 SD below the mean for age, a finding considered to denote heterozygocity for their molecular defect disease. The significant correlation (p less than 0.001) between serum GH binding protein activity and IGF-I levels supports this conclusion. The ability to define heterozygotes of Laron type dwarfism will be helpful in genetic counselling.