ANDROGEN METABOLISM IN CHILDHOOD

这是在其第32个资助年度提交的修订赠款。 主要强调基因型与表型的相关性 结合分子和临床研究。两个单基因缺陷将 研究：21-羟化酶缺乏症，导致疾病 先天性肾上腺增生（CAR）和11 β-HSD 2缺乏症， 表观盐皮质激素过量（Apparent Mineralocorticoid Excess，AME） 我们招募了一位医学信息学专家， 描述CAH患者纵向数据的数据库 纽博士的追随者超过30年了数据库包括广泛的 对357名CAR患者的临床和分子遗传学研究， 将进行分析，以确定接受治疗的患者的最终结局 糖皮质激素先天性肾上腺增生症产前治疗的远期效果 将研究地塞米松对认知和行为的影响。我们有 在一个门诺派血亲家庭中发现了一种新的温和的AME形式 并有机会调查其他2000人中是否有- 成员会众在11 HSDB 2基因突变类似于我们的 病人我们还将研究盐皮质激素的作用， 糖皮质激素对体内和体外11 β- HSD 2缺乏症总的来说，我们建议继续调查 类固醇疾病与我们新成立的团队组成的博士。 New，Wilson，Obeid，Hanauske-Abel，Newfield，and Meyer-Bahlburg.我们 最近的进展证明这个小组有能力推进这项工作 始于33年前我们集团的优势是：1）富人 转介到本科作类固醇诊断的病人来源 疾病和高血压。2)我们是美国唯一一个。 常规进行CAR的产前诊断和治疗， 已经积累了大量的产前治疗的婴儿， study. 3)由于New博士自1955年以来一直留在NYH-CMC， 跟踪从出生到成年的类固醇疾病。很少有 一组病人被如此仔细地记录下来， 临床、激素和分子遗传学数据。4)威尔逊博士带来了 在分子遗传学方面具有特殊的专业知识， 临床团队5)Ranauske-Abel博士增加了一个新的维度， 类固醇激素促纤维化和抗纤维化作用的研究 患者和培养的人类细胞中。6)和谐互动 分子遗传学家、生物化学家、精神内分泌学家， 在处理病人方面有丰富经验的临床医生。

This is a revised submission of a grant in its 32nd year of funding. The primary emphasis is on the correlation of genotype of phenotype combining molecular and clinical studies. Two monogenic defects will be studied: 21-hydroxylase deficiency, which results in the disease Congenital Adrenal Hyperplasia (CAR), and 11beta-HSD2 deficiency, which is the cause of the disease Apparent Mineralocorticoid Excess (AME). We have recruited a medical informatics specialist who has established a database describing the longitudinal data of patients with CAH followed by Dr. New for over 30 years. The database includes extensive clinical and molecular genetics studies of 357 patients with CAR and will be analyzed to determine the final outcome of patients treated with glucocorticoid. The long term effects of prenatal treatment of CAH with dexamethasone on cognition and behavior will be studied. We have discovered a new mild form of AME in a consanguineous Mennonite family and have an opportunity to investigate whether others in their 2,000- member congregation have mutations in the 11HSDB2 gene similar to our patient. We will also study the effect of mineralocorticoids and glucocorti-coids on collagen synthesis in vivo and in vitro in 11beta- HSD2 deficiency. Overall, we propose to continue the investigation of steroid disorders with our newly constituted team consisting of Drs. New, Wilson, Obeid, Hanauske-Abel, Newfield, and Meyer-Bahlburg. Our recent progress attests that this team is capable of advancing the work started 33 years ago. The strengths of our group are: 1) The rich source of patients referred to our division for diagnosis of steroid disorders and hypertension. 2) We are the only group in the U.S.A. routinely carrying out prenatal diagnosis and treatment of CAR and thus have accumulated a large population of prenatally-treated infants to- study. 3) As Dr. New has remained at NYH-CMC since 1955, patients with steroid disorders from birth to adulthood are followed. Rarely has a group of patients been so carefully documented continuously with clinical, hormonal, and molecular genetics data. 4) Dr. Wilson brings special expertise in molecular genetics and works compatibly with the clinical teams. 5) Dr. Ranauske-Abel adds a new dimension, with the investigation of pro-and antifibrotic effects of steroid hormones in patients and in cultured human cells. 6) The harmonious interaction of molecular geneticists, biochemists, psychoendocrinologists, and clinicians with great experience in dealing with patients.