Sanchez J E, Perera E, Baumbach L, Cleveland W W
Department of Pediatrics, University of Miami School of Medicine, Florida 33136, USA.
J Clin Endocrinol Metab. 1998 Nov;83(11):4079-83. doi: 10.1210/jcem.83.11.5238.
Homozygous or compound heterozygous mutations in the GH receptor (GHR) gene result in GH insensitivity syndrome. Previous reports have shown that some heterozygous mutations may induce a partial insensitivity to GH, but others appear to have limited effect on growth. To investigate further these observations, we analyzed the GHR gene in 17 subjects with idiopathic short stature (ISS). All subjects had a height 2 SD or more below the mean and/or abnormal growth velocity. In addition, serum GH levels were 10 ng/mL or more and insulin-like growth factor I levels were normal or low. A novel heterozygous mutation resulting in a valine to isoleucine change (V144I) in exon 6 in the extracellular domain was found in one subject. His mother and one brother had significant short stature and also had the identical mutation. Affected family members also had a polymorphism in exon 6 of the GHR gene, which has been present in other subjects who had short stature and heterozygous mutations of the GHR gene. The other subjects with ISS had normal GHR genes. However, eight subjects had neutral polymorphisms distributed throughout the GHR locus. Accumulating evidence suggests that GHR gene mutations account for up to 5% of all ISS patients. These mutations should be considered when other causes of short stature have been eliminated.
生长激素受体（GHR）基因的纯合或复合杂合突变会导致生长激素不敏感综合征。先前的报道显示，一些杂合突变可能会导致对生长激素的部分不敏感，但其他一些突变对生长的影响似乎有限。为了进一步研究这些观察结果，我们分析了17例特发性身材矮小（ISS）患者的GHR基因。所有患者的身高比平均身高低2个标准差或更多，和/或生长速度异常。此外，血清生长激素水平为10 ng/mL或更高，胰岛素样生长因子I水平正常或偏低。在一名患者中发现了一种新的杂合突变，该突变导致细胞外结构域第6外显子中的缬氨酸变为异亮氨酸（V144I）。他的母亲和一个兄弟身材显著矮小，并且也有相同的突变。受影响的家庭成员在GHR基因第6外显子中也有一个多态性，其他身材矮小且GHR基因存在杂合突变的患者也有这种多态性。其他ISS患者的GHR基因正常。然而，8名患者在整个GHR基因座中存在中性多态性。越来越多的证据表明，GHR基因突变在所有ISS患者中占比高达5%。在排除了其他身材矮小的原因后，应考虑这些突变。
