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Laron综合征是一种常染色体隐性遗传病,生长激素受体(GHR)基因缺陷是导致Laron综合征的主要病因。Laron综合征主要临床特征为生后严重的生长落后伴特殊面容,血生化特点为高生长激素(GH)、低胰岛素样生长因子-I(IGF-I)和低胰岛素样生长因子结合蛋白-3(IGFBP-3)。该研究报道一家系2例Laron综合征患者的临床特点及GHR基因突变。这两个病人为同胞姐弟。弟弟8岁,身高80.0cm(-8.2SDS),姐姐11岁,身高96.6cm(-6.8SDS)。他们出生体重和身长无特殊,自生后出现生长落后,身高明显落后于同龄正常儿童,并均呈现了典型Laron综合征外貌特征:身材矮、肥胖、前额突出、大眼睛、塌鼻梁、头发稀软。这两个病人空腹血清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和生长激素结合蛋白(GHBP)低于检测线。其中1例(8岁男孩)胰岛素和可乐定刺激后GH峰值大于350ng/mL,给予重组人生长激素治疗1年,身高由治疗前的80.0cm增加至83.3cm。GHR基因序列测定结果显示2例患者均存在外显子4上第65位氨基酸的纯合突变S65H(TCA→CCA),为新发现的突变。Laron综合征患者存在特殊的面貌特征,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突变可能是这两位Laron综合征患者的致病原因。
Laron syndrome is an autosomal recessive disease, and growth hormone receptor (GHR) gene defect is the leading cause of Laron syndrome. The main clinical features of Laron syndrome are severe postnatal growth accompanied by special facial features. The biochemical features of Laron syndrome are high growth hormone (GH), low insulin-like growth factor-I (IGF-I) and low insulin-like growth factor binding protein-3 (IGFBP-3). The study reports the clinical features and GHR mutations of two patients with Laron syndrome in a family. These two patients are fellow siblings. His younger brother is 8 years old, height 80.0cm (-8.2SDS), sister 11 years old, height 96.6cm (-6.8SDS). Their birth weight and length of no exception, after their own growth appears backward, height significantly behind the normal children of the same age, and showed the appearance of a typical Laron syndrome: short stature, obesity, prominent forehead, big eyes, collapsed nose, thin hair soft . Fasting serum GH was significantly higher in both patients than in normal children, fasting serum IGF-I was significantly lower than same-age normal children of the same age, plasma IGFBP-3 and growth hormone binding protein (GHBP) below the detection line. One patient (8-year-old boy) had a GH peak greater than 350 ng / mL after stimulation with insulin and clonidine, a 1-year treatment with recombinant human growth hormone, and an increase in height from 80.0 cm to 83.3 cm before treatment. The results of GHR gene sequencing showed that homozygous mutation S65H (TCA → CCA) of amino acid 65 of exon 4 existed in both cases, which was a newly discovered mutation. Laron syndrome patients with special facial features, combined with blood GH, IGF-I, IGFBP-3 and GHBP determination can be a clear diagnosis. The S65H mutation in exon 4 of the GHR gene may be responsible for the pathogenesis of these two Laron syndrome patients.