Otsuka T, Iwatani N, Kodama M, Sakakida M, Shichiri M, Jinno Y, Niikawa N, Miike T
Department of Child Development, Kumamoto University School of Medicine, Japan.
Jpn J Hum Genet. 1997 Jun;42(2):323-9. doi: 10.1007/BF02766954.
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 template, all exons and flanking portions of introns of GHR 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 a BanI restriction site. Since this substitution was not detected by a BanI 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 of GHR 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).
在拉龙综合征患者中已鉴定出生长激素（GH）受体基因（GHR）的缺失和点突变。我们报告了在日本拉龙综合征患者中首次检测到GHR突变。以日本女性患者的基因组DNA为模板，通过聚合酶链反应（PCR）扩增GHR的所有外显子和内含子侧翼部分。PCR产物测序表明，该患者在第4内含子的第一个位置存在G到A的纯合替代。这种替代与在一名西班牙患者和一名北欧患者中检测到的相同。碱基变化发生在第4内含子的5'剪接共有序列处，导致BanI限制性位点消失。由于在85名对照个体中通过BanI限制性分析未检测到这种替代，因此它更可能是一种与疾病相关的剪接突变而非多态性。预计我们患者中的突变会破坏GHR第4内含子的原始5'剪接位点并产生一个新的隐蔽剪接位点，导致异常的mRNA加工以及生长激素结合蛋白（GHBP）缺乏GH结合活性。
