遗传性肾病的早期识别允许个性化管理,澄清亲属的风险,和计划生育指导。遗传性疾病诊断不足,在不区分诊断特征的肾衰竭患者中,对遗传性疾病的识别尤其具有挑战性。为了应对这一挑战,这项研究的主要目的是确定病因不明的肾衰竭患者中基因诊断的比例,使用全基因组测序(WGS)。一组多达100名病因不明的澳大利亚肾衰竭患者,发病年龄<50岁,并由研究人员小组批准,将通过全国18个中心招募。临床认可的WGS将进行针对与遗传性肾脏疾病相关的~388个基因的优先列表的分析。主要结果是通过WGS接受分子诊断的患者比例(诊断率)与常规治疗(没有进一步的诊断研究)相比。参与者调查将在同意后进行,测试结果返回后和1年后。在没有诊断或诊断不确定的地方,未来的研究基因组学将考虑识别候选基因和已知基因中的新致病变异。所有结果将通过招募临床医生和/或肾脏遗传学诊所传达给参与者。该研究已获得伦理批准(HREC/16/MH/251),并已获得当地现场治理批准。这项研究的未来结果将被传播,并告知对病因不明的肾衰竭的潜在单基因贡献的实际理解。这些发现预计将影响临床实践和医疗保健政策。
■[https://dora.健康。qld.gov.au],标识符[HREC/16/MH/251]。
Early identification of genetic kidney disease allows personalised management, clarification of risk for relatives, and guidance for family planning. Genetic disease is underdiagnosed, and recognition of genetic disease is particularly challenging in patients with kidney failure without distinguishing diagnostic features. To address this challenge, the primary aim of this
study is to determine the proportion of genetic diagnoses amongst patients with kidney failure of unknown aetiology, using whole genome sequencing (WGS). A cohort of up to 100 Australian patients with kidney failure of unknown aetiology, with onset <50 years old and approved by a panel of
study investigators will be recruited via 18 centres nationally. Clinically accredited WGS will be undertaken with analysis targeted to a priority list of ∼388 genes associated with genetic kidney disease. The primary outcome will be the proportion of patients who receive a molecular diagnosis (diagnostic rate) via WGS compared with usual -care (no further diagnostic investigation). Participant surveys will be undertaken at consent, after test result return and 1 year subsequently. Where there is no or an uncertain diagnosis, future research genomics will be considered to identify candidate genes and new pathogenic variants in known genes. All results will be relayed to participants via the recruiting clinician and/or kidney genetics clinic. The
study is ethically approved (HREC/16/MH/251) with local site governance approvals in place. The future results of this
study will be disseminated and inform practical understanding of the potential monogenic contribution to kidney failure of unknown aetiology. These findings are anticipated to impact clinical practice and healthcare policy.
UNASSIGNED: [https://dora.health.qld.gov.au], identifier [HREC/16/MH/251].