Diseases Of Aminoacid Transport: Genetic, Molecular and Biochemical Studies

氨基酸运输疾病：遗传、分子和生化研究

• 批准号: nhmrc : 402730
• 负责人: A/Pr Juleen Cavanaugh
• 金额: $ 26.28万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/diseases-aminoacid-transport-biochemical-studies/95157
• 关键词: Diseases; Aminoacid; Transport; Genetic; Molecular

Aminoacids are essential building blocks of all living things. They are taken up and retained in the body by highly specific pumps on the surface of cells. By understanding the mechanisms that control aminoacids, we will not only uncover pathways common to normal biology but also shed light on mechanisms of disease in humans. Specifically, the aminoacidurias include a number of inherited diseases of aminoacid transport that result in failure of uptake and retention of particular aminoacids. Hartnup disease is an inherited disorder of neutral aminoacid transport that can lead to a sun-sensitive skin rash, difficulties in controlling movements and walking and other neurological symptoms including mental retardation. A major feature of Hartnup disease is its clinical variability. We have recently identified the main genetic cause for Hartnup disease, and named the gene SLC6A19. We wish to examine whether the clinical variability observed is a consequence of genetic changes and variability in SLC6A19 and other possible genes. Two other aminoacidurias to be studied are dicarboxylic aminoaciduria and iminoglycinuria; both of which are also variable in their clinical consequences ranging from normality to mental retardation. Owing to the relative rarity of these disorders, we are fortunate to have exclusive access to individuals identified by the largest neonatal screening programme for aminoacidurias in the world, based in Canada, and other clinical cohorts within Australia. We will undertake genetic testing to localise and-or confirm the gene(s) involved in these diseases for the first time anywhere and then seek to explain their clinical variability based on functional analyses. We have established a team of researchers with complementary skills from three sites comprising the Australian Aminoaciduria Consortium. Outcomes from this project should impact on the causes and possible therapies for other important medical diseases including motor neurone disease.

氨基酸是所有生物必不可少的组成部分。它们被细胞表面高度特异的泵吸收并保留在体内。通过了解控制氨基酸的机制，我们不仅将发现正常生物学共同的途径，而且还将阐明人类的疾病机制。具体地说，氨基酸尿症包括一些遗传性氨基酸转运疾病，这些疾病导致特定氨基酸的摄取和保留失败。Hartnup病是一种遗传性中性氨基酸运输障碍，可导致日光敏感型皮疹、运动和行走控制困难以及包括智力低下在内的其他神经症状。Hartnup病的一个主要特征是其临床变异性。我们最近确定了Hartnup病的主要遗传原因，并将基因命名为SLC6A19。我们希望检查观察到的临床变异性是否是SLC6A19和其他可能基因的遗传变化和变异性的结果。另外两种要研究的氨基酸尿症是二羧酸氨基酸尿症和亚氨酸甘氨酸尿症；这两种尿症的临床后果也各不相同，从正常到智力低下不等。由于这些疾病的相对罕见，我们幸运地独家接触到设在加拿大的世界上最大的氨基酸尿症新生儿筛查计划以及澳大利亚境内的其他临床队列所确定的个人。我们将进行基因测试，首次在任何地方定位和-或确认与这些疾病有关的基因(S)，然后基于功能分析寻求解释它们的临床变异性。我们已经建立了一个具有互补技能的研究团队，他们来自三个地点，组成了澳大利亚氨基酸尿症联合会。该项目的结果将对包括运动神经元疾病在内的其他重要医学疾病的病因和可能的治疗方法产生影响。