Laron综合征家系患者生长激素受体基因突变分析

The growth hormone receptor gene mutations in a Chinese family with Laron syndrome

目的研究Laron综合征患者的临床特点及生长激素受体(GHR)的基因突变。方法对一家系中2例表现为身材明显落后的患儿进行研究,分别进行体格测量和GH-IGF-I轴功能测定。提取外周血白细胞基因组DNA,运用聚合酶链式反应(PCR)扩增GHR基因第2～9外显子及其两侧的侧翼序列,直接进行测序,将所测结果与正常人GHR基因序列进行对比,确定突变位点和突变类型。对突变基因均经2次测定证实。结果2例患儿自出生后身长明显落后于同龄儿童,呈现Laron综合征的独特面貌,空腹血清GH值均明显高于正常儿童。空腹血清IGF-I明显低于同年龄同性别正常儿童。血浆IGFBP-3和GHBP低于检测线。GHR基因序列测定结果显示2例患儿均存在外显子4上第65为氨基酸的纯合突变S65H,为新发现突变。结论Laron综合征患者存在典型的面貌特征,结合血GH、IGF-I、IGFBP-3和GHBP测定可以明确诊断。GHR基因外显子4上S65H突变可能是该Laron综合征患者的致病原因。[临床儿科杂志,2007,25(12):971-973]

Objectives To study growth hormone receptor （GHR） gene mutation in two patients with Laron syndrome and review their clinical features. Methods Two children with sever short stature from the same Chinese family were selected in the study. Height and weight were measured. The GH-IGF-I axis function was evaluated. Genomic DNA from peripheral blood leucocytes was collected. Exons 2-9 of GHR gene and the flanking intron sequences were amplified with polymerase chain reaction （PCR）, and sequenced directly. Results were compared with normal GHR gene sequence for identification of the mutation type and site. Mutations were confirmed by repeating the gene amplification and sequencing. Results Height of the patients was significantly delayed than age-matched children after birth and typical appearance of Laron syndrome were observed. Their basal GH levels were higher than normal. The IGF-I levels were lower than normal. The IGFBP-3 and GHBP were undetectable. Gene mutation analysis revealed that two patients had the same homozygous mutation of S65H in exon 4, which was a novel gene mutation. Conclusions A definite diagnosis of Laron syndrome can be made according to the typical clinical features and serum levels of GH, IGF-I, IGFBP-3 and GHBP. The S64H mutation might be the cause of Laron syndrome in these two patients.