{"title":"A feasible molecular diagnostic strategy for rare genetic disorders within resource-constrained environments.","authors":"Maria Mabyalwa Mudau, Heather Seymour, Patracia Nevondwe, Robyn Kerr, Careni Spencer, Candice Feben, Zané Lombard, Engela Honey, Amanda Krause, Nadia Carstens","doi":"10.1007/s12687-023-00674-8","DOIUrl":null,"url":null,"abstract":"<p><p>Timely and accurate diagnosis of rare genetic disorders is critical, as it enables improved patient management and prognosis. In a resource-constrained environment such as the South African State healthcare system, the challenge is to design appropriate and cost-effective assays that will enable accurate genetic diagnostic services in patients of African ancestry across a broad disease spectrum. Next-generation sequencing (NGS) has transformed testing approaches for many Mendelian disorders, but this technology is still relatively new in our setting and requires cost-effective ways to implement. As a proof of concept, we describe a feasible diagnostic strategy for genetic disorders frequently seen in our genetics clinics (RASopathies, Cornelia de Lange syndrome, Treacher Collins syndrome, and CHARGE syndrome). The custom-designed targeted NGS gene panel enabled concurrent variant screening for these disorders. Samples were batched during sequencing and analyzed selectively based on the clinical phenotype. The strategy employed in the current study was cost-effective, with sequencing and analysis done at USD849.68 per sample and achieving an overall detection rate of 54.5%. The strategy employed is cost-effective as it allows batching of samples from patients with different diseases in a single run, an approach that can be utilized with rare and less frequently ordered molecular diagnostic tests. The subsequent selective analysis pipeline allowed for timeous reporting back of patients results. This is feasible with a reasonable yield and can be employed for the molecular diagnosis of a wide range of rare monogenic disorders in a resource-constrained environment.</p>","PeriodicalId":46965,"journal":{"name":"Journal of Community Genetics","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858011/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Community Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s12687-023-00674-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/10 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Timely and accurate diagnosis of rare genetic disorders is critical, as it enables improved patient management and prognosis. In a resource-constrained environment such as the South African State healthcare system, the challenge is to design appropriate and cost-effective assays that will enable accurate genetic diagnostic services in patients of African ancestry across a broad disease spectrum. Next-generation sequencing (NGS) has transformed testing approaches for many Mendelian disorders, but this technology is still relatively new in our setting and requires cost-effective ways to implement. As a proof of concept, we describe a feasible diagnostic strategy for genetic disorders frequently seen in our genetics clinics (RASopathies, Cornelia de Lange syndrome, Treacher Collins syndrome, and CHARGE syndrome). The custom-designed targeted NGS gene panel enabled concurrent variant screening for these disorders. Samples were batched during sequencing and analyzed selectively based on the clinical phenotype. The strategy employed in the current study was cost-effective, with sequencing and analysis done at USD849.68 per sample and achieving an overall detection rate of 54.5%. The strategy employed is cost-effective as it allows batching of samples from patients with different diseases in a single run, an approach that can be utilized with rare and less frequently ordered molecular diagnostic tests. The subsequent selective analysis pipeline allowed for timeous reporting back of patients results. This is feasible with a reasonable yield and can be employed for the molecular diagnosis of a wide range of rare monogenic disorders in a resource-constrained environment.
对罕见遗传疾病的及时准确诊断至关重要,因为它可以改善患者的管理和预后。在资源有限的环境中,如南非国家医疗系统,面临的挑战是设计合适且具有成本效益的检测方法,为非洲血统的广泛疾病患者提供准确的基因诊断服务。下一代测序(NGS)已经改变了许多孟德尔疾病的检测方法,但这项技术在我们的环境中仍然相对较新,需要成本效益高的方法来实施。作为概念的证明,我们描述了一种可行的诊断策略,用于治疗我们遗传学诊所中常见的遗传疾病(RA病、Cornelia de Lange综合征、Treacher-Collins综合征和CHARGE综合征)。定制设计的靶向NGS基因小组能够同时筛查这些疾病的变体。在测序过程中分批取样,并根据临床表型进行选择性分析。当前研究中采用的策略具有成本效益,测序和分析费用为每个样本849.68美元,总体检测率为54.5%。采用的策略成本效益高,因为它可以在一次运行中对不同疾病患者的样本进行批处理,这种方法可用于罕见且不太频繁的分子诊断测试。随后的选择性分析管道允许及时报告患者结果。这是可行的,产率合理,可用于在资源有限的环境中对各种罕见的单基因疾病进行分子诊断。
期刊介绍:
The Journal of Community Genetics is an international forum for research in the ever-expanding field of community genetics, the art and science of applying medical genetics to human communities for the benefit of their individuals.
Community genetics comprises all activities which identify persons at increased genetic risk and has an interest in assessing this risk, in order to enable those at risk to make informed decisions. Community genetics services thus encompass such activities as genetic screening, registration of genetic conditions in the population, routine preconceptional and prenatal genetic consultations, public education on genetic issues, and public debate on related ethical issues.
The Journal of Community Genetics has a multidisciplinary scope. It covers medical genetics, epidemiology, genetics in primary care, public health aspects of genetics, and ethical, legal, social and economic issues. Its intention is to serve as a forum for community genetics worldwide, with a focus on low- and middle-income countries.
The journal features original research papers, reviews, short communications, program reports, news, and correspondence. Program reports describe illustrative projects in the field of community genetics, e.g., design and progress of an educational program or the protocol and achievement of a gene bank. Case reports describing individual patients are not accepted.