New growth hormone receptor exon 9 mutation causes genetic short stature

A novel form of congenital growth hormone insensitivity syndrome (GHIS), wh ich lacks the classic phenotype associated with this condition, is describe d. Dominant inheritance is shown to result from a heterozygous 876-1 G to C transversion of the 3' splice acceptor site preceding exon 9 in the growth hormone receptor (GHR) gene. The result of this mutation is a severely tru ncated cytoplasmic domain of the GHR. which is incapable of transmitting a signal. The mutant receptor is shown to form a heterodimer with the wild-ty pe GHR, the activity of which is inhibited in a dominant-negative manner.