HETEROZYGOUS MUTATION IN THE WSXWS EQUIVALENT MOTIF OF THE GROWTH-HORMONE RECEPTOR IN A CHILD WITH POOR RESPONSE TO GROWTH-HORMONE THERAPY

Besides complete GH insensitivity syndrome (GHIS) described by Laron, clinical and molecular evidences have accumulated concerning partial G HIS. We studied GH receptor (GHR) gene in children who show poor respo nse to GH treatment and detected a patient with a heterozygous mutatio n in exon 7 leading to the (YH)-H-222 substitution. This missense muta tion, located in the YGEFS motif of the GHR equivalent to the WSXWS mo tif highly conserved throughout all members of the cytokine receptor f amily, has not been described so far. Although we cannot conclude on t he deleterious effect of this mutation, there are several lines of evi dence suggesting that it could account for the partial GH insensitivit y: (i) hormonal data including IGF-I generation test; (ii) molecular d ata - no other mutation was identified in the coding sequence, the fat her who has the same mutation is short, the brother did not inherit th e mutated allele and was of normal height. (C) 1998 Churchill Livingst one.