Genetic Characterization of Essential Hyperhidrosis

原发性多汗症的遗传特征

• 批准号: 6474309
• 负责人: Gary D Swergold
• 金额: $ 19.42万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6474309
• 关键词: DNA; autonomic nervous system; autosomal dominant trait; clinical research; disease /disorder etiology; disease /disorder proneness /risk; family genetics; gene expression; genetic mapping; genetic susceptibility; human genetic material tag; human subject; interview; molecular cloning; neurogenetics; patient oriented research; questionnaires; sweat; sweat gland disorder; sympathectomy

Description: The goals of this investigation are to characterize the genetics of Essential Hyperhidrosis (EH), and to develop an improved understanding of the regulation of sweating by the autonomic nervous system. EH is a relatively common disorder in which patients' experience excessive sweating from their palms and soles. Patients with EH sweat profusely and, as a result, have difficulty with many activities of normal daily living, including social interactions, writing, using keyboards, and using musical instruments. It is not uncommon for the sweat to actually drip from the hands onto the floor. Many patients find EH so socially disabling and non-invasive therapies so ineffective that they undergo thoracic sympathectomy. The pathophysiology of EH is largely unknown; however, abundant evidence indicates that it is primarily a disorder of the autonomic nervous system. A genetic etiology and a dominant mode of inheritance have been suggested by several surgical studies, documenting a high-rate of affected first-degree family members, an equal number of affected male and female patients, and an early age-of-onset in nearly all patients. Despite this, no family study or report on the mode of inheritance of EH has ever been published. In addition, the control of sweating by the autonomic nervous system is poorly understood. We will recruit families with EH based on the identification of probands who have undergone thoracic sympathectomy. Detailed medical and family histories will be obtained, and a DNA sample will be collected from probands and family members. A state-of-the-art Skinos SKD-2000 skin moisture meter will be used to obtain measurements of resting and stimulated palmar, and forehead sweating from all study participants under a standardized protocol. The use of a specific questionnaire (the Hyperhidrosis Scale) and sweat measurements for the genetic investigation of EH will be validated. A detailed description of the EH phenotype will be developed, and a segregation analysis will be performed to determine the mode of inheritance. Simulation will be performed to determine the sample size and power for future linkage analysis. This will be followed by the mapping and cloning of the EH gene in follow-on studies. This study represents a rare opportunity to investigate a previously neglected neurogenetic condition. Knowledge of the gene responsible for EH will improve our understanding of the disease, and may permit the design of more effective therapies. Most importantly, understanding the etiology of EH may open a new window of understanding into the organization and regulation of the autonomic nervous system, and the regulation of body temperature and sweating.

产品描述： 本研究的目的是描述原发性多汗症（EH）的遗传学特征，并进一步了解自主神经系统对出汗的调节。高血压是一种相对常见的疾病， 手掌和脚底出汗过多。EH患者大量出汗 因此，在许多正常的日常生活活动中有困难， 包括社交、写作、使用键盘和使用音乐 仪器.汗水从手上滴下来并不罕见 扔到地板上许多患者发现高血压是如此的社会残疾和非侵入性 治疗如此无效，他们接受胸交感神经切除术。的 EH的病理生理学在很大程度上是未知的;然而，大量证据表明， 它主要是一种自主神经系统的紊乱。遗传 病因学和显性遗传模式已提出了几个 手术研究，记录了高比例的一级家庭受影响 成员，同等数量的受影响的男性和女性患者， 几乎所有患者的发病年龄。尽管如此，没有家庭研究或报告， EH的遗传方式曾被发表过。此外，控制 自主神经系统对出汗的影响知之甚少。我们将 招募EH家族，基于对先证者的识别， 接受了胸交感神经切除术详细的医疗和家庭史将 获得，并从先证者和家庭成员中收集DNA样本。 将使用最先进的Skinos SKD-2000皮肤水分仪， 测量休息和刺激手掌，和额头出汗，从所有 研究参与者根据标准化协议。使用特定 问卷（多汗症量表）和汗液测量的遗传 将对EH的调查进行验证。EH的详细描述 将开发表型，并进行分离分析， 确定继承方式。将进行模拟以确定 未来连锁分析的样本量和功效。随后将 EH基因的定位和克隆为后续研究奠定基础。本研究 这是一个难得的机会来调查一个以前被忽视的 神经遗传病对EH基因的了解将提高 我们对疾病的了解，并可能允许设计更有效的 治疗最重要的是，了解高血压的病因可能会打开一个新的 了解自主神经系统的组织和调节的窗口 神经系统，以及体温和出汗的调节。