THE GROWTH-HORMONE RECEPTOR GENE MUTATION OF A JAPANESE PATIENT WITH LARON-SYNDROME

Deletions and point mutations of the growth hormone (GH) receptor gene (GHR) have been identified in patients with Laron syndrome. We report the first detection of the GHR mutation among Japanese patients with Laron syndrome. Using the Japanese female patient's genomic DNA as a t emplate, all exons and flanking portions of introns of GHR were amplif ied by polymerase chain reaction (PCR). Sequencing of the PCR products showed that the patient was homozygous for a G to A substitution at t he first position of intron 4. This substitution was same as that dete cted in a Spanish patient and a north European patient. The base chang e occurred at the 5' splice consensus sequence of intron 4, resulting in the abolition of a BanI restriction site. Since this substitution w as not detected by a BanI restriction analysis in 85 control individua ls, it is more likely a disease-related splice mutation than a polymor phism. The mutation in our patient was predicted to destroy the origin al 5' splice site of intron 4 of GHR and to produce a new cryptic spli ce site, leading to abnormal mRNA processing and a lack of GH binding activity of GH-binding protein (GHBP).