Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia
Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia
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DOI：
10.1210/jc.85.10.3636
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发表时间：
2000-10-01
影响因子：
5.8
通讯作者：
Miller, WL
中科院分区：
文献类型：
--
作者：
Bose, HS;Sato, S;Miller, WL
先天性类脂质肾上腺增生（类脂质CAH）是CAH最严重的形式，由类固醇生成急性调节蛋白（星星）突变引起。脂质CAH在日本人、韩国人和巴勒斯坦阿拉伯人中很常见，但在其他地方很少见。我们描述了6例类脂CAH患者：4名日本人，1名巴勒斯坦人和1名危地马拉土著美国人。所有的经典临床表现正常的女性外生殖器在两个遗传性别，严重的糖皮质激素和盐皮质激素缺乏症出现在第一个月的生活。相当危险的是，一个病人的肾上腺显示小的计算机断层扫描。星星基因在所有6名患者中进行了表征。其中3名日本患者为常见日本突变Q258X的复合杂合子，并伴有3种不同的新型移码突变：第4名日本患者为突变R182L纯合子，这在巴勒斯坦患者中很常见，但以前在日本患者中未描述过。我们的巴勒斯坦和美洲原住民患者都是新型移码突变的纯合子。因此，我们发现了五个新的移码突变，但没有新的氨基酸替换（错义）突变。这与星星蛋白中只有少量残基对生物活性至关重要的观点是一致的。由于星星突变，在遗传学证实的类脂CAH患者中，小肾上腺的断层扫描结果表明，这种疾病的临床表现比以前认识到的要广泛得多。
Congenital lipoid adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is caused by mutations in the steroidogenic acute regulatory protein (StAR). Lipoid CAH is common among the Japanese, Korean, and Palestinian Arab populations, but is rare elsewhere. We describe six patients with lipoid CAH: four Japanese, one Palestinian, and one Guatemalan Native American. All had classical clinical presentations of normal female external genitalia in both genetic sexes, with severe glucocorticoid and mineralocorticoid deficiency presenting in the first month of life. Quite atypically, one patient had small adrenal glands shown by computed tomographic scanning. The StAR genes were characterized in all six patients. Three of the Japanese patients were compound heterozygotes for the common Japanese mutation Q258X in association with three different novel frameshift mutations: the fourth Japanese patient was homozygous for the mutation R182L, which is common among Palestinian patients but has not been described previously in a Japanese patient. Our Palestinian and Native American patients were each homozygous for novel frameshift mutations. Thus we have found five new frameshift mutations, but no new amino acid replacement (missense) mutations. This would be consistent with the view that only a small number of residues in the StAR protein are crucial for biological activity. The tomographic finding of small adrenals in a patient with genetically proven lipoid CAH due to a StAR mutation suggests a substantially broader spectrum of clinical findings in this disease than has been appreciated previously.