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 substit utions in the intracellular region of the human GH receptor in a child with growth failure and clinical features of the Laron syndrome. At t he second position of codon 422 a G to T transversion changes a cystei ne residue to phenylalanine, whereas at the first nucleotide of codon 561 an alteration from C to A leads to the substitution of threonine f or proline. Direct analysis of exon 10 of the GH receptor gene showed that both nucleotide substitutions reside on the same chromosome and w ere inherited from the patient's mother. Evaluation of DNA from 10 add itional prospectively recruited children with growth failure and a cli nical picture similar to the index case did not reveal any nucleotide alterations in codons 422, 560, or 561. These observations represent t he first demonstration of variation within the intracytoplasmic part o f the human GH receptor and indicate that mutations occurring at multi ple locations within the receptor gene may lead to the same clinical p henotype.