Molecular basis for familial isolated growth hormone deficiency.

Nuclear DNA from four individuals with familial isolated growth hormone (somatotropin) deficiency (IGHD) type A was studied by restriction endonuclease analysis. By using 32P-labeled human growth hormone (hGH) cDNA sequences as a probe, patterns seen after various digestions indicated that these individuals were homozygous for a deletion of at least 7.5 kilobases (kb) of DNA. This deletion includes the gene that encodes the normal growth hormone but does not include the variant growth hormone gene. Restriction patterns of DNAs from all family members agreed with an autosomal recessive mode of inheritance of the deletion that correlates with the clinical phenotype. Furthermore, independent assortment of the two types of hGH genes suggests that these genes are nonallelic. These findings indicate that, in these families, IGHD type A is caused by deletion of the normal hGH genes and that this disorder can occur in the presence of variant hGH genes.