Prospect of genetic disorders in Saudi Arabia

Frontiers in Genetics

Genetics

Ahmed Alfares¹  Raniah S. Alotibi²  Taghrid Aloraini³  Amerh S. Alqahtani⁴  Yara Alassali⁵  Bader Alhaddad⁶  Mariam M. Al Eissa⁷  Fahad Almsned⁸ 

[1] Centre for Genomic Medicine, King Faisal Specialist Hospital and Research Centre, 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;Division of Translational Pathology, Department of Laboratory Medicine, King Abdulaziz Medical City, Department of Genetics, King Abdullah Specialized Children Hospital, MNGHA, Riyadh, Saudi Arabia;Division of Translational Pathology, Department of Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia;Department of Genetics, King Abdullah Specialized Children Hospital, MNGHA, Riyadh, Saudi Arabia;Medical Genetics Department, King Saud Medical City, Riyadh, Saudi Arabia;Medical School, AlFaisal University, Riyadh, Saudi Arabia;Molecular Genetics Department, King Saud Medical City, Riyadh, Saudi Arabia;Laboratory Medicine Department, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al Khobar, Saudi Arabia;Public Health Authority, Public Health Lab, Molecular Genetics Laboratory, Riyadh, Saudi Arabia;Medical School, AlFaisal University, Riyadh, Saudi Arabia;Research Centre, King Fahad Specialist Hospital in Dammam (KFSH-D), Dammam, Saudi Arabia;Population Health Management, Eastern Health Cluster, Dammam, Saudi Arabia;Research and Development Department, NovoGenomics, Riyadh, Saudi Arabia;

关键词: single nucleotide variant;    neurodevelopmental disorders;    exome sequencing;    genome sequencing;    panel;    diagnostic yield;    Saudi Arabia;   

DOI  :  10.3389/fgene.2023.1243518

 received in 2023-06-20, accepted in 2023-08-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: 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.Methodology: 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.Result: 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 DNAJC12, SLC19A3, and ALDH7A1, and the presence of the founder effect variant in SKIC2. Neurodevelopmental disorders were the main phenotype for which genetics studies were required (35.7%).Conclusion: 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.

【 授权许可】

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Copyright © 2023 Alqahtani, Alotibi, Aloraini, Almsned, Alassali, Alfares, Alhaddad and Al Eissa.