TRANSTHYRETIN IN FAMILIAL AMYLOIDOTIC POLYNEUROPHATHY

描述：(改编自申请者的摘要)遗传形式 家族性淀粉样变性多发性神经病是一种常染色体病 与蛋白质突变形式相关的显性遗传性疾病 转甲状腺素(TTR，又称前白蛋白)。这是一种罕见的晚发性 一种遗传性疾病，由于外周和外周原因导致迅速恶化 中国自主神经病变与心肌病 生活。它提出了一个问题，一个异常基因是如何从 十年后，生育会引发疾病。活组织检查证明淀粉样蛋白 证词在第一次症状出现之前就开始了。 已鉴定出六种不同形式的淀粉样前体TTR.每个人 涉及正常127个氨基酸中的单一氨基酸替代 TTR链。在他们来自28个家庭的FAP患者中， 申请者最近发现了一个新的变种，并有其他变种。 具有未知类型变体的家族。它们的表型和表型不同 种族起源于彼此，并且没有一个已知的Ttr 变种。申请者建议检查他们的DNA和/或血浆 导致淀粉样蛋白沉积的TTR变异并确定 这种突变的基因测试技术。一名患者患有 纯合突变模式将提供独特的机会来检查 它的蛋白质分解，并开发出一种抗体，只对突变的蛋白质。 他们计划测试这一假设，即临床症状的变化、年龄 在发病时，疾病的进展可能由其他因素解释 TTR基因的单核苷酸突变。他们的初步数据 提示突变的Ttr的β形成在以下情况下发生了根本变化 用蛋白水解酶人中性粒细胞弹性酶消化。这些 研究将扩展到来自患有 出现症状前的FAP，并在已知比例的正常和 分离混合物中的变种Ttr。了解致病原因 前体TTR加工成淀粉样蛋白的机制 他们预计，纤维将有助于最终确定 治疗干预。

DESCRIPTION: (Adapted from the applicant's abstract) The hereditary form of amyloidosis, familial amyloidotic polyneuropathy (FAP) is an autosomal dominantly inherited condition associated with a mutant form of the protein transthyretin (TTR, also called pre-albumin). It is a rare late-onset genetic disease which results in rapid deterioration due to peripheral and autonomic neuropathy and cardiomyopathy in the third or fourth decade of life. It raises the question of how an abnormal gene which is present from birth produces disease a decade later. Biopsies have proven that amyloid deposition begins just prior to the time of first symptoms. Six variant forms of the amyloid precursor TTR had been identified. Each involves a single amino acid substitution in the normal 127 amino acid chain of TTR. In their population of patients from 28 families with FAP, the applicants have recently identified one new variant and have other families with variants of unknown type. They differ phenotypically and in ethnic origin from each other and do not have one of the known TTR variants. The applicants proposed to examine their DNA and/or plasma for TTR variations that have resulted in amyloid deposition and to determine techniques for the genetic testing of that mutation. One patient with a homozygous mutant pattern will provide the unique opportunity to examine its proteolysis and to develop an antibody only to the mutant protein. They plan to test the hypothesis that variations in clinical symptoms, age at onset, and disease progression may be explained by factors other than the single nucleotide mutation in the TTR gene. Their preliminary data suggest a radical change in the beta formation of the mutant TTR when digested with a proteolytic enzyme human neutrophil elastase. These studies will be extended to TTR proteins from individuals who have pre-symptomatic FAP and carried out on known proportions of normal and variant TTR in the isolated mixture. Understanding the pathogenetic mechanisms involved in the processing of the precursor TTR into amyloid fibrils, they anticipate, will aid in the ultimate goal of defining treatment intervention.