Alqahtani Amerh S, Alotibi Raniah S, Aloraini Taghrid, Almsned Fahad, Alassali Yara, Alfares Ahmed, Alhaddad Bader, Al Eissa Mariam M
Medical Genetics Department, King Saud Medical City, Riyadh, Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia.
Front Genet. 2023 Sep 20;14:1243518. doi: 10.3389/fgene.2023.1243518. eCollection 2023.
Rare diseases (RDs) create a massive burden for governments and families because sufferers of these diseases are required to undergo long-term treatment or rehabilitation to maintain a normal life. In Saudi Arabia (SA), the prevalence of RDs is high as a result of cultural and socio-economic factors. This study, however, aims to shed light on the genetic component of the prevalence of RDs in SA. A retrospective study was conducted between September 2020 and December 2021 at King Saud Medical City, a tertiary hospital of the Ministry of Health (MOH), SA. A total of 1080 individuals with 544 potentially relevant variants were included. The index was 738, and the samples were tested in a commercialized laboratory using different molecular techniques, including next-generation sequencing. A total of 867 molecular genetics tests were conducted on 738 probands. These tests included 610 exome sequencing (ES) tests, four genome sequencing (GS) tests, 82 molecular panels, 106 single nucleotide polymorphism (SNP) array, four methylation studies, 58 single-gene studies and three mitochondrial genome sequencing tests. The diagnostic yield among molecular genetics studies was 41.8% in ES, 24% in panels, 12% in SNP array and 24% in single gene studies. The majority of the identified potential variants (68%) were single nucleotide variants (SNV). Other ascertained variants included frameshift (11%), deletion (10%), duplication (5%), splicing (9%), in-frame deletion (3%) and indels (1%). The rate of positive consanguinity was 56%, and the autosomal recessive accounted for 54%. We found a significant correlation between the ES detection rate and positive consanguinity. We illustrated the presence of rare treatable conditions in , , and and the presence of the founder effect variant in Neurodevelopmental disorders were the main phenotype for which genetics studies were required (35.7%). This is the sixth-largest local study reporting next-generation sequencing. The results indicate the influence of consanguineous marriages on genetic disease and the burden it causes for the Kingdom of SA. This study highlights the need to enrich our society's knowledge of genetic disorders. We recommend utilising ES as a first-tier test to establish genetic diagnosis in a highly consanguineous population.
罕见病给政府和家庭带来了沉重负担，因为这些疾病的患者需要长期接受治疗或康复以维持正常生活。在沙特阿拉伯（SA），由于文化和社会经济因素，罕见病的患病率很高。然而，本研究旨在阐明沙特阿拉伯罕见病患病率的遗传因素。2020年9月至2021年12月期间，在沙特阿拉伯卫生部（MOH）的三级医院沙特国王医疗城进行了一项回顾性研究。共纳入了1080名携带544个潜在相关变异的个体。索引病例为738例，样本在一家商业化实验室使用包括下一代测序在内的不同分子技术进行检测。对738名先证者共进行了867次分子遗传学检测。这些检测包括610次外显子组测序（ES）检测、4次基因组测序（GS）检测、82次分子检测板、106次单核苷酸多态性（SNP）阵列检测、4次甲基化研究、58次单基因研究和3次线粒体基因组测序检测。分子遗传学研究中的诊断率在ES中为41.8%，在检测板中为24%，在SNP阵列中为12%，在单基因研究中为24%。大多数已鉴定的潜在变异（68%）为单核苷酸变异（SNV）。其他确定的变异包括移码突变（11%）、缺失（10%）、重复（5%）、剪接突变（9%）、框内缺失（3%）和插入缺失（1%）。近亲结婚率为56%，常染色体隐性遗传占54%。我们发现ES检测率与近亲结婚呈显著相关性。我们阐明了在[具体疾病名称1]、[具体疾病名称2]和[具体疾病名称3]中存在罕见的可治疗疾病，以及在[具体疾病名称4]中存在奠基者效应变异。神经发育障碍是需要进行遗传学研究的主要表型（35.7%）。这是报告下一代测序的第六大本地研究。结果表明近亲结婚对遗传疾病的影响及其给沙特阿拉伯王国带来的负担。本研究强调了丰富我们社会对遗传疾病知识的必要性。我们建议将ES作为高度近亲结婚人群中进行遗传诊断的一线检测方法。
