Growth hormone receptor gene mutations in two Italian patients with Laron Syndrome
Growth hormone receptor gene mutations in two Italian patients with Laron Syndrome
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DOI：
10.1007/bf03346320
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发表时间：
2007-05-01
影响因子：
5.4
通讯作者：
Bona, G.
中科院分区：
文献类型：
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作者：
Fassone, L.;Corneli, G.;Bona, G.
Laron综合征(LS)是一种由于生长激素受体(GHR)基因或受体后信号通路中的分子缺陷而导致的生长激素不敏感的疾病。我们报告了两名来自西西里的意大利女孩被诊断为LS的分子特征。GHR基因的DNA测序显示存在不同的无义突变，发生在相同的背景单倍型中。分子缺陷发生在GHR的胞外区，导致提前终止信号和截断的非功能受体。在1例患者中，外显子6的纯合子G到T颠换导致180密码子的GAA到TAA突变(E180X)，而在第二例患者中检测到外显子7的纯合子C到T转换，导致第217密码子的CGA到TAA替换(R217X)。两位先证者分别在第6外显子和第10外显子上表现出Gly168Gly和Ile544Leu的纯合子状态。E180X代表了GHR基因的一种新的缺陷，而R217X突变之前已经在几名来自不同种族背景但都来自地中海和中东地区国家的患者中被报道过。
Laron Syndrome (LS) represents a condition characterized by GH insensitivity caused by molecular defects in the GH receptor (GHR) gene or in the post-receptor signalling pathway. We report the molecular characterization of two unrelated Italian girls from Sicily diagnosed with LS. The DNA sequencing of the GHR gene revealed the presence of different nonsense mutations, occurring in the same background haplotype. The molecular defects occurred in the extracellular domain of the GHR leading to a premature termination signal and to a truncated non-functional receptor. In one patient, a homozygous G to T transversion, in exon 6, led to the mutation GAA to TAA at codon 180 (E180X), while in the second patient a homozygous C to T transition in exon 7 was detected, causing the CGA to TAA substitution at codon 217 (R217X). Both probands presented the polymorphisms Gly168Gly and Ile544Leu in a homozygous state in exons 6 and 10, respectively. The E180X represents a novel defect of the GHR gene, while the R217X mutation has been previously reported in several patients from different ethnic backgrounds but all from countries located in the Mediterranean and Middle Eastern region.