Genetic Characterization of Essential Hyperhidrosis

原发性多汗症的遗传特征

• 批准号: 6624378
• 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/6624378
• 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.

描述： 这项研究的目的是确定原发性多汗症 (EH) 的遗传学特征，并加深对自主神经系统出汗调节的了解。 EH 是一种相对常见的疾病，患者会经历 手掌和脚底出汗过多。 EH患者多汗 因此，许多正常日常生活活动都有困难， 包括社交互动、写作、使用键盘和使用音乐 仪器。汗水从手上滴下来的情况并不少见 到地板上。许多患者发现 EH 具有社交障碍且非侵入性 治疗无效，以至于他们接受了胸交感神经切除术。这 EH 的病理生理学在很大程度上尚不清楚；然而，大量证据表明 它主要是自主神经系统的疾病。遗传性 一些人提出了病因学和主要的遗传模式 外科研究，记录了一级家庭受影响的比例很高 成员，同等数量的受影响的男性和女性患者，以及早期 几乎所有患者的发病年龄。尽管如此，还没有家庭研究或报告 EH的遗传方式已被公开。此外，控制 人们对自主神经系统出汗的机制知之甚少。我们将 根据先证者的身份招募患有 EH 的家庭 接受了胸交感神经切除术。详细的病史和家族史将 获得，并将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 皮肤水分计来获得 测量休息和受刺激的手掌和前额出汗的情况 根据标准化方案研究参与者。使用特定的 遗传问卷（多汗症量表）和汗液测量 EH 调查将得到验证。 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。接下来将是 后续研究中EH基因的定位和克隆。这项研究 提供了一个难得的机会来调查以前被忽视的问题 神经遗传状况。对导致 EH 的基因的了解将会提高 我们对疾病的了解，并可能允许设计更有效的 疗法。最重要的是，了解 EH 的病因可能会开辟一个新的领域。 了解自主组织和调节的窗口 神经系统，以及体温和出汗的调节。

项目成果

Diagnosis of palmar hyperhidrosis via questionnaire without physical examination.

无需体检，通过问卷调查诊断手汗症。

• DOI: 10.1007/s10286-009-0006-5
• 发表时间: 2009
• 期刊: Clinical autonomic research : official journal of the Clinical Autonomic Research Society
• 作者: Keller,StevenM;Bello,Riccardo;Vibert,Betsy;Swergold,Gary;Burk,Robert
• 通讯作者: Burk,Robert