New growth hormone receptor exon 9 mutation causes genetic short stature.
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.
Ayling
R M
RM
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, University of London, UK.
Ross
R J
RJ
Towner
P
P
Von Laue
S
S
Finidori
J
J
Moutoussamy
S
S
Buchanan
C R
CR
Clayton
P E
PE
Norman
M R
MR
D001483:Base Sequence; D001827:Body Height / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D005799:Genes, Dominant; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011986:Receptors, Somatotropin / Q000235:genetics*
D011986:Receptors, Somatotropin