Heterozygous mutations of growth hormone receptor gene in children with idiopathic short stature
Heterozygous mutations of growth hormone receptor gene in children with idiopathic short stature
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DOI：
10.1016/j.ghir.2005.08.004
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发表时间：
2005-12-01
影响因子：
1.4
通讯作者：
Coviello, DA
中科院分区：
文献类型：
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作者：
Bonioli, E;Tarò, M;Coviello, DA
目的：特发性矮小(ISS)指的是：(A)身高低于平均值两个标准差以上；(B)身高速度正常或缓慢；(C)出生体重正常；(D)无特定内分泌异常；(E)没有慢性身体或心理疾病的证据。有人认为生长激素受体基因杂合性突变导致的部分生长激素不敏感可能是导致ISS的原因。设计和方法：对37例ISS患者进行GHR基因检测(SSCP和直接测序)。结果：我们观察到了先前描述的密码子168第3位的突变A>；G(GGA>；GGG)，确定了37例患者中22例(12例纯合子和10例杂合子)和23例对照组(16例纯合子和7例杂合子)的G168G同义改变。患者组和对照组的相对等位基因频率相似。在一名ISS患者中，我们发现了94密码子第3位的一种新的转换T>；C(Tgt>；TGC)，确定了同义改变C94C。在另一例患者中，我们发现了第144位密码子第2位的一种新的杂合性转换T>；C(GTC>；GCC)，确定了错义突变V144A，这些突变在100条对照染色体中未发现。结论：GHR基因杂合突变在意大利ISS患者中并不常见，他们被选为GH水平足够高的患者。然而，在37名ISS患者中观察到的2个突变的发生率(即5%)与以前文献中报道的没有什么不同。(C)2005爱思唯尔有限公司。保留所有权利。
Objective: The term idiopathic short stature (ISS) describes children: (a) whose height is more than two standard deviations below the mean; (b) with normal or slow height velocity; (c) of normal birth weight, (d) showing an absence of specific endocrine abnormalities; and (e) having no evidence of chronic physical or psychological illness. It has been suggested that partial growth hormone (GH) insensitivity due to heterozygous mutations of the GH Receptor gene may account for some cases of ISS.Design and methods: GHR gene was investigated (SSCP assay and direct sequencing) in 37 ISS patients. Fifty controls were recruited from the same geographic area as the patients; age and gender were stratified to match controls to patients.Results: We observed the previously described transition A > G (GGA > GGG) of position 3 of codon 168, determining the synonymous change G168G in 22 of 37 patients (12 homozygous and 10 heterozygous) and in 23 of 50 controls (16 homozygous and 7 heterozygous). The relative allele frequency was similar in patients and in controls. In one ISS patient we identified a novel transition T > C (TGT > TGC) of position 3 of codon 94, determining the synonymous change C94C. In another patient we demonstrated a novel heterozygous transition T > C (GTC > GCC) of the position 2 of codon 144, determining the missense mutation V144A, These mutations were not found in 100 control chromosomes.Conclusions: Heterozygous mutations of the GHR gene are uncommon in Italian ISS patients, who are selected for adequate GH levels. However the observed incidence of 2 mutations out of 37 ISS patients (i.e., 5%) is not different from the one previously reported in the literature. (c) 2005 Elsevier Ltd. All rights reserved.