Division of Endocrinology, University Hospital, Federal University of Sergipe, Rua Claudio Batista s/n, Aracaju, Sergipe, 49060-100, Brazil.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine Baltimore, Baltimore, MD, 21287, USA.
Rev Endocr Metab Disord. 2021 Mar;22(1):81-89. doi: 10.1007/s11154-020-09591-4. Epub 2020 Sep 16.
Since 1994, we have been studying an extended kindred with 105 subjects (over 8 generations) residing in Itabaianinha County, in the Brazilian state of Sergipe, who have severe isolated GH deficiency (IGHD) due to a homozygous inactivating mutation (c.57 + 1G > A) in the GH releasing hormone (GHRH) receptor (GHRHR) gene. Most of these individuals have never received GH replacement therapy. They have low GH, and very low and often undetectable levels of serum IGF-I. Their principal physical findings are proportionate short stature, doll facies, high-pitched-voice, central obesity, wrinkled skin, and youthful hair with delayed pigmentation, and virtual absence of graying. The newborns from this cohort are of normal size, indicating that GH is not needed for intra-uterine growth. However, these IGHD individuals exhibit a myriad of phenotypic changes throughout the body, with a greater number of beneficial than harmful consequences. This GHRH signal disruption syndrome has been a valuable model to study the GH roles in body size and function. This reviews summarized the findings we have reported on this cohort.
自 1994 年以来，我们一直在研究一个扩展的家族，该家族有 105 名成员（超过 8 代）居住在巴西塞尔希培州的伊塔拜亚宁哈县，他们患有严重的孤立性生长激素缺乏症（IGHD），这是由于生长激素释放激素（GHRH）受体（GHRHR）基因中的纯合失活突变（c.57 + 1G > A）引起的。这些个体中的大多数从未接受过生长激素替代治疗。他们的 GH 水平低，血清 IGF-I 水平非常低，且常常检测不到。他们的主要身体特征是匀称的身材矮小、娃娃脸、高音调的声音、中心性肥胖、皮肤起皱和年轻的头发，色素沉着延迟，几乎没有白发。该队列中的新生儿大小正常，表明 GH 对于宫内生长是不需要的。然而，这些 IGHD 个体表现出全身多种表型变化，有益的后果比有害的后果多。这种 GHRH 信号中断综合征一直是研究 GH 在体型和功能中的作用的有价值的模型。这篇综述总结了我们对该队列的研究结果。
