In the last few years, our knowledge of genetically determined causes of short stature has greatly increased by reports of challenging patients, who offered the opportunity to study genes that play a role in growth. Since the first paper that showed the etiology of Laron syndrome [Godowski PJ, et al: Proc Natl Acad Sci USA 1989;86:8083-8087], many mutations in the growth hormone (GH) receptor have been identified. Recently, new mutations or deletions have been found in several components of the GH-insulin-like growth factor-I (IGF-I) axis: a homozygous mutation of the GH1 gene, resulting in a bio-inactive GH; mutations in the STAT5b gene, which plays a major role in the GH signal transduction; a homozygous missense mutation in the IGF-I gene; heterozygous mutations in the IGF-I receptor gene and a homozygous deletion of the acid-labile subunit gene. In this mini review, we describe the clinical and biochemical features of these genetic defects. Genetic analysis has become essential in the diagnostic workup of a patient with short stature. However, regarding the time consuming nature of molecular analysis, it is important to carefully select the patient for specific genetic evaluation. To help in this selection process, we developed flowcharts, based on the recently described patients, that can be used as guidelines in the diagnostic process of patients with severe short stature of unknown origin.

译文

在过去的几年中,由于有挑战性的患者的报道,我们对基因确定的矮小原因的了解大大增加了,他们提供了研究在生长中起作用的基因的机会。自从第一篇显示拉隆综合征病因的论文 [Godowski PJ等人: Proc Natl Acad Sci USA 1989;86:8083-8087] 以来,已经鉴定出生长激素 (GH) 受体的许多突变。最近,在GH-胰岛素样生长因子-I (igf-i) 轴的几个组成部分中发现了新的突变或缺失: GH1基因的纯合突变,导致了具有生物活性的GH; STAT5b基因的突变,在GH信号转导中起主要作用; Igf-i基因中的纯合错义突变; Igf-i受体基因中的杂合突变和酸不稳定亚基基因的纯合缺失。在这篇小型综述中,我们描述了这些遗传缺陷的临床和生化特征。基因分析在身材矮小的患者的诊断检查中已变得至关重要。但是,关于分子分析的耗时性质,重要的是要仔细选择患者以进行特定的遗传评估。为了帮助这一选择过程,我们根据最近描述的患者开发了流程图,该流程图可作为不明原因严重矮小患者诊断过程的指南。

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