Fintini Danilo, Salvatori Roberto, Salemi Souzan, Otten Barto, Ubertini Graziamaria, Cambiaso Paola, Mullis Primus E
Division of Endocrinology, Department of Medicine and Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Horm Res. 2006;65(2):76-82. doi: 10.1159/000091033. Epub 2006 Jan 18.
Autosomal-dominant isolated GH deficiency (IGHD) is a rare disorder that is commonly believed to be due to heterozygous mutations in the GH-1 gene (GH-1). These mutations cause the production of a protein that affects the release of the product of the normal allele. Rarely, heterozygous mutations in the gene encoding for HESX-1 gene (HESX-1) may cause autosomal-dominant IGHD, with penetrance that has been shown to be variable in both humans and mice.
We have sequenced the whole GH-1 in the index cases of 30 families with autosomal-dominant IGHD. In all the families other possible causes of GH deficiency and other pituitary hormones deficits were excluded. We here describe the clinical, biochemical and radiological picture of the families without GH-1 mutations. In these families, we also sequenced the HESX-1.
The index cases of the five families with autosomal-dominant IGHD had normal GH-1, including the intronic sequences. They had no HESX-1 mutations.
This study shows that GH-1 mutations are absent in 5/30 (16.6%) of the families with autosomal-dominant IGHD and raises the possibility that mutations in other gene(s) may be involved in IGHD with this mode of transmission.
常染色体显性遗传性孤立性生长激素缺乏症（IGHD）是一种罕见疾病，通常认为是由于生长激素-1基因（GH-1）的杂合突变所致。这些突变导致产生一种影响正常等位基因产物释放的蛋白质。编码HESX-1基因（HESX-1）的基因中罕见的杂合突变可能导致常染色体显性IGHD，其外显率在人类和小鼠中均显示出可变。
我们对30个常染色体显性IGHD家族的先证者进行了GH-1全序列测序。在所有家族中，排除了生长激素缺乏和其他垂体激素缺乏的其他可能原因。我们在此描述了无GH-1突变家族的临床、生化和放射学表现。在这些家族中，我们也对HESX-1进行了测序。
5个常染色体显性IGHD家族的先证者GH-1正常，包括内含子序列。他们没有HESX-1突变。
本研究表明，在30个常染色体显性IGHD家族中有5个（16.6%）不存在GH-1突变，并增加了其他基因的突变可能参与这种遗传方式的IGHD的可能性。
