一个Laron综合征家系患者临床特点和生长激素受体基因突变分析(英文)

Clinical features and growth hormone receptor gene mutations of patients with Laron syndrome from a Chinese family

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 disorder caused by defects of growth hormone receptor （GHR） gene. It is characterized by severe postnatal growth retardation and characteristic facial features as well as high circulating levels of growth hormone （GH） and low levels of insulin-like growth factor I （IGF-I） and insulin-like growth factor binding protein-3 （IGFBP-3）. This report described the clinical features and GHR gene mutations in 2 siblings with Laron syndrome in a Chinese family. Their heights and weights were in the normal range at birth, but the growth was retarded after birth. When they presented to the clinic, the heights of the boy （8 years old） and his sister （11 years old） were 80.0 cm （ - 8.2 SDS） and 96.6 cm （ - 6.8 SDS） respectively. They had typical appearance features of Laron syndrome such as short stature and obesity, with protruding forehead, saddle nose, large eyes, sparse and thin silky hair and high-pitched voice. They had higher basal serum GH levels and lower serum levels of IGF-I, IGFBP-3 and growth hormone binding protein（GHBP） than normal controls. The peak serum GH level after colonidine and insulin stimulations in the boy was over 350 ng/mL. Mter one-year rhGH treatment, the boy＇s height increased from 80.0 cm to 83.3 cm. The gene mutation analysis revealed that two patients had same homozygous mutation of $65 H （TCA →CCA） in exon 4, which is a novel gene mutation. It was concluded that a definite diagnosis of Laron syndrome can be made based on characteristic appearance features and serum levels of GH, IGF-I, IGFBP-3 and GHBP. The S65H mutation might be the cause of Laron syndrome in the two patients.