New growth hormone receptor exon 9 mutation causes genetic short stature

Ayling RM, Ross RJM, Towner P, Von Laue S, Finidori J, Moutoussamy S, Buchanan CR, Clayton PE, Norman MR. Acta Pa; diatr 1999; Suppl 428: 168–72. Stockholm. ISSN 0803–5326. A novel form of congenital growth hormone insensitivity syndrome (GHIS), which lacks the classic phenotype associated with this condition, is described. 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 truncated cytoplasmic domain of the GHR, which is incapable of transmitting a signal. The mutant receptor is shown to form a heterodimer with the wild-type GHR, the activity of which is inhibited in a dominant-negative manner. □Dominant-negative mutation, growth hormone receptor