특발성 저신장증환아에서 성장호르몬 수용체의 돌연변이 및 부분적 성장호르몬 저항성

Abstract

Purpose : Children with idiopathic short stature(ISS) are classified on the ba_is of exclusion criteria. Short stature with normal or increased circulating growth hormone(GH and low IGF-I levels indicates that partial growth hormone insensitivity(GHI) may play a role in ISS. The present study was performed to investigate whether partial GHI is observed in children with idiopathic short stature and whether partial GHI is related to growth hormon( receptor, GHR) defect. Methods : Twenty-five children with ISS were studied and 30 no -mal children were enrolled as control. Anthropometric measurement and IGF-I generation test were performed. The GHR gene was amplified *by PCR, from leukocyte-derived DNA and sequenced directly. Results : IGF-I level was increased after GH treatment, but there was no significant correlation between delta IGF-I and delta HTSDS, as well as between delta IGFBP-3 and delta HTSDS indicating partial GHI in children with ISS. When GHR genes were analyzed. polymorphism was observed. That is, adenine which is third base for 168 th amino acid was guanine. Furthermore this finding was observed in 100% of 55 children examined, which was a rather higher incidence compared to previous reports from other country. The first base of 526 th amino acid was either adenine or cytosine or heterozygous of adenine and cytosine, suggesting an occurrence of I526L variant. Deletions of one or two bases in flanking region of exon 3 and 8 were confirmed in Koreans, the same as it occurs in Japanese. There are differences in the sequences of human GHR gene among different ethnic populations. Wide variations of phenotype in ISS cannot clearly be explained by GHR gene alone. Variations or polymorphism of GHR genes remains to be functionally analysed. Conclusion : ISS might be due to the partial GHI which is resuls from mutation of GHR genes.