创新背景

2018年，英国卫生部宣布了NHS基因组医学服务，允许罕见疾病患者读取他们的整个基因密码，希望提供急需的诊断。

然而，对这些数据的解释可能是极具挑战性的，许多患有复杂、罕见遗传疾病的人仍然没有得到引起他们问题的分子原因的答案。

创新过程

在这项新研究中，研究人员试图为此类患者提供更好的接受基因诊断的机会。

为此，他们测试了如何使用由专家医生、生物信息学家和科学家组成的基因组医学团队来提高NHS诊断实验室的能力，而不仅仅是标准的半自动数据分析。伦敦大学学院的研究小组重新评估了未确诊的病例，以找出可能有助于指导进一步、更个性化分析的线索。他们随后应用了额外的生物信息学方法，使用先进的计算机技术来识别患者DNA中的基因改变，这些改变可能会导致疾病，但在常规检测中被忽略了。

所有参与的患者都已经通过英格兰基因组公司的“10万基因组计划”（新NHS基因组医疗服务的重要先驱）接受了全基因组测序，试图找到他们疑似原发性线粒体疾病(PMD)的遗传原因。PMD是一组遗传多样性的重要遗传疾病，影响儿童和成人，与广泛的医疗问题、严重残疾和寿命缩短有关。这项研究的个性化方法几乎使确诊患者的比例翻了一番，从16.7%增至31.4%。它还在另外3.9%的患者中检测到潜在的致病变异，现在可以针对这些患者进行进一步的研究。

在这项研究中，每一个新的基因诊断都对病人的护理有直接影响。这包括针对心脏问题、听力损失和糖尿病的额外检查，以及参加临床试验的机会。

这项工作在为患者开发最大化基因组分析益处的最佳方法方面向前迈出了重要一步。它清楚地表明，通过将基因组分析的自动化方法与熟练的多学科团队的数据解释相结合，诊断率翻了一番。这是一个重要的发现，它将影响基因组医学诊断服务在全球范围内的发展。

创新关键点

所有参与的患者都已经通过英格兰基因组公司的“10万基因组计划”（新NHS基因组医疗服务的重要先驱）接受全基因组测序。

创新价值

接受基因诊断很重要，因为它使患者能够获得计划生育、专门试管受精和药物试验的机会。它还可以对已知的疾病并发症进行有针对性的筛查，并进行药物研究。

为患有罕见、复杂疾病的儿童和成人做出诊断的过程可能是一个非常漫长的过程，而基因组医学为帮助实现这一目标提供了一种革命性的强大工具。

这项研究强调了临床专家和遗传科学家在解释基因组测序结果方面合作的重要性，以最大限度地提高诊断的机会，从而帮助指导医疗管理和治疗选择。

Innovative, customized and personalized whole genome sequencing could double the diagnosis rate of rare diseases

In the new study, the researchers tried to give such patients better access to genetic diagnosis.

To that end, they tested how a genomic medicine team of expert doctors, bioinformatists and scientists could be used to boost the capabilities of NHS diagnostic laboratories beyond the standard semi-automatic data analysis. The UCL team reassessed undiagnosed cases for clues that might help guide further, more personalised analysis. They then applied additional bioinformatics methods, using advanced computer technology to identify genetic alterations in a patient's DNA that might contribute to the disease but were missed in routine testing.

All the patients involved have already had their whole genomes sequenced through Genome England's 100,000 Genomes Project, a key precursor to the new NHS genomic medical service, in an attempt to find the genetic cause of their suspected primary mitochondrial disease (PMD). PMD is a genetically diverse group of important genetic disorders that affect both children and adults and are associated with a wide range of medical problems, severe disability and shortened life expectancy. The study's personalized approach nearly doubled the proportion of patients diagnosed, from 16.7 percent to 31.4 percent. It also detected potential disease-causing variants in an additional 3.9 percent of patients, which can now be targeted for further study.

Each new genetic diagnosis in the study had a direct impact on patient care. This includes additional screening for heart problems, hearing loss and diabetes, as well as the opportunity to participate in clinical trials.

This work is an important step forward in developing the best way for patients to maximize the benefits of genomic analysis. It clearly shows that diagnosis rates have doubled by combining automated methods of genomic analysis with data interpretation by skilled multidisciplinary teams. This is an important finding that will influence the development of genomic medicine diagnostic services on a global scale.