No correlation of growth hormone receptor gene mutation P561T with body height

Analysis of the growth hormone receptor (GHR) gene in GH insensitivity syndrome revealed various mutations, mainly in the gene encoding the extracellular domain of GHR. On the other hand, the mutation of the gene encoding the cytoplasmic domain of GHR was not found. We have reported, in the cytoplasmic domain of a GHR gene, mutation P561T in a patient with Noonan syndrome who showed a blunted insulin-like growth factor I (IGF-I) response to an acute injection of GH. However, her mother possessing the same mutation had no growth failure. To clarify the significance of the GHR gene mutation P561T, 96 volunteers (41 males aged 21-80 years; 55 females, aged 20-80 years, were tested for the presence of this mutation. By the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, three of the 41 males and 11 of the 55 females examined revealed heterozygous missense mutation P561T. The body height (cm) was 168 +/- 5.3 (mean +/- SD) in three males with the mutation and 164.1 +/- 5.8 in 38 males without the mutation. The difference between them was not statistically significant. The body height in 11 females with the mutation was 152.6 +/- 5.4, which did not differ significantly from 151.3 +/- 6.2 in 44 females without the mutation. These findings suggest that the heterozygous missense mutation P561T in the cytoplasmic domain of GHR does not play a significant role in determining the final body height.