Amino acid substitutions in the intracellular part of the growth hormone receptor in a patient with the Laron syndrome

By complementary DNA cloning we have identified two amino acid substitutions in the intracellular region of the human GH receptor in a child with growth failure and clinical features of the Laron syndrome. At the second position of codon 422 a G to T transversion changes a cysteine residue to phenylalanine, whereas at the first nucleotide of codon 561 an alteration from C to A leads to the substitution of threonine for proline. Direct analysis of exon 10 of the GH receptor gene showed that both nucleotide substitutions reside on the same chromosome and were inherited from the patient's mother. Evaluation of DNA from 10 additional prospectively recruited children with growth failure and a clinical picture similar to the index case did not reveal any nucleotide alterations in codons 422, 560, or 561. These observations represent the first demonstration of variation within the intracytoplasmic part of the human GH receptor and indicate that mutations occurring at multiple locations within the receptor gene may lead to the same clinical phenotype.