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 theGHR mutation among Japanese patients with Laron syndrome. Using the Japanese female patient’s genomic DNA as a template, all exons and flanking portions of introns ofGHR were amplified by polymerase chain reaction (PCR). Sequencing of the PCR products showed that the patient was homozygous for a G to A substitution at the first position of intron 4. This substitution was same as that detected in a Spanish patient and a north European patient. The base change occurred at the 5′ splice consensus sequence of intron 4, resulting in the abolition of aBanI restriction site. Since this substitution was not detected by aBanI restriction analysis in 85 control individuals, it is more likely a disease-related splice mutation than a polymorphism. The mutation in our patient was predicted to destroy the original 5′ splice site of intron 4 ofGHR and to produce a new cryptic splice site, leading to abnormal mRNA processing and a lack of GH binding activity of GH-binding protein (GHBP).