{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:40:46Z","timestamp":1784346046515,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KFSH&amp;RC","award":["RAC# 2241173"],"award-info":[{"award-number":["RAC# 2241173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Chromosomal aneuploidy, characterized by an abnormal number of chromosomes, represents a significant cause of genetic disorders. While karyotyping and chromosomal microarray analysis (CMA) are established diagnostic approaches, they are limited by cost and extended turnaround times. Advances in exome sequencing (ES) bioinformatics enable detection of chromosomal aneuploidy alongside single-nucleotide variant analysis. This study explores the utility of clinical ES for the detection of aneuploidies. Method: We analyzed exome sequencing data (2023\u20132024) from samples positive for Trisomy 21 (n = 27), Trisomy 18 (n = 4), Turner syndrome (n = 3), and Klinefelter syndrome (n = 2) from our clinical ES cohort (n = 10,000). Results: The results obtained were concordant with copy number variants (CNVs) identified by clinical testing. Conclusion: In conclusion, our findings suggest that exome sequencing offers a rapid and viable approach for the detection of chromosomal aneuploidy, potentially reducing turnaround time and associated costs.<\/jats:p>","DOI":"10.3390\/genes16090992","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:10:36Z","timestamp":1756080636000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Detection of Chromosomal Aneuploidy Using Exome Sequencing"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-6122","authenticated-orcid":false,"given":"Mohamed H.","family":"Al-Hamed","sequence":"first","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2999-2229","authenticated-orcid":false,"given":"Sateesh","family":"Maddirevula","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Moghrabi","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Aldahmesh","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-1859","authenticated-orcid":false,"given":"Abdullah H.","family":"Alfalah","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebtissal","family":"Khouj","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-8970","authenticated-orcid":false,"given":"Norah","family":"Altuwaijri","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midrar","family":"Alhossiny","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2961-5733","authenticated-orcid":false,"given":"Faiqa","family":"Imtiaz","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4222-0952","authenticated-orcid":false,"given":"Ahmed","family":"Alfares","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory Department, Genomic Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, X., Zhang, J., Song, Z., Wang, S., Gao, Y., Wang, J., Luo, Y., Niu, Z., and Yue, X. (2014). Detection of chromosomal aneuploidy in human preimplantation embryos by next-generation sequencing. Biol. Reprod., 90.","DOI":"10.1095\/biolreprod.113.116459"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/ng0496-368","article-title":"Karyotyping human chromosomes by combinatorial multi-fluor FISH","volume":"12","author":"Speicher","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/jcmm.16080","article-title":"Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis","volume":"25","author":"Zhang","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1093\/rpd\/ncac264","article-title":"Fluorescence in situ hybridisation for interphase chromosomal aberration-based biological dosimetry","volume":"199","author":"Meher","year":"2023","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1097\/01.gim.0000186545.83160.1e","article-title":"American College of Medical Genetics Professional Practice and Guidelines Committee. American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation","volume":"7","author":"Shaffer","year":"2005","journal-title":"Genet. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1056\/NEJMra1312543","article-title":"Diagnostic clinical genome and exome sequencing","volume":"370","author":"Biesecker","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic and Functional Approaches to Understanding Cancer Aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3390\/jcm3030747","article-title":"Exome Sequencing in Fetuses with Structural Malformations","volume":"3","author":"Mackie","year":"2014","journal-title":"J. Clin. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Borrell, A., Ordo\u00f1ez, E., Pauta, M., Ota\u00f1o, J., Paz-Y-Mi\u00f1o, F., de Almeida, M., Le\u00f3n, M., and Cirigliano, V. (2023). Prenatal Exome Sequencing Analysis in Fetuses with Various Ultrasound Findings. J. Clin. Med., 13.","DOI":"10.3390\/jcm13010181"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S0140-6736(18)32042-7","article-title":"Whole-exome sequencing in the evaluation of fetal structural anomalies: A prospective cohort study","volume":"393","author":"Petrovski","year":"2019","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gilissen, C., Hoischen, A., Brunner, H.G., and Veltman, J.A. (2011). Unlocking Mendelian disease using exome sequencing. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-9-228"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing","volume":"22","author":"Koboldt","year":"2012","journal-title":"Genome Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/s41436-020-0771-z","article-title":"Systematic evidence-based review: Outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability","volume":"22","author":"Malinowski","year":"2020","journal-title":"Genet. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kuchar\u00edk, M., Budi\u0161, J., H\u00fdblov\u00e1, M., Min\u00e1rik, G., and Szemes, T. (2021). Copy Number Variant Detection with Low-Coverage Whole-Genome Sequencing Represents a Viable Alternative to the Conventional Array-CGH. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040708"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tommel, J., Kenis, D., Lambrechts, N., Brohet, R.M., Swysen, J., Mollen, L., Hoefmans, M.-J.F., Pusparum, M., Evers, A.W.M., and Ertaylan, G. (2023). Personal Genomes in Practice: Exploring Citizen and Healthcare Professionals\u2019 Perspectives on Personalized Genomic Medicine and Personal Health Data Spaces Using a Mixed-Methods Design. Genes, 14.","DOI":"10.3390\/genes14040786"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e32063","DOI":"10.1002\/ajmg.c.32063","article-title":"Beyond chromosome analysis: Additional genetic testing practice in a Down syndrome clinic","volume":"193","author":"Harisinghani","year":"2023","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"a005231","DOI":"10.1101\/mcs.a005231","article-title":"Disease-associated mosaic variation in clinical exome sequencing: A two-year pediatric tertiary care experience","volume":"6","author":"Miller","year":"2020","journal-title":"Mol Case Stud."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5604\/12321966.1196874","article-title":"Next generation sequencing for preimplantation genetic testing of blastocysts aneuploidies in women of different ages","volume":"23","author":"Lukaszuk","year":"2016","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s13023-024-03340-5","article-title":"Genetic analysis of pregnancy loss and fetal structural anomalies by whole exome sequencing","volume":"19","author":"Xiang","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zare, F., and Nabavi, S. (2019, January 7\u201310). Copy Number Variation Detection Using Total Variation. Proceedings of the BCB \u201919: 10th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics, Niagara Falls, NY, USA.","DOI":"10.1145\/3307339.3342181"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/bioinformatics\/btr707","article-title":"Read count approach for DNA copy number variants detection","volume":"28","author":"Magi","year":"2012","journal-title":"Bioinformatics"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/9\/992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:46Z","timestamp":1760034886000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/9\/992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["genes16090992"],"URL":"https:\/\/doi.org\/10.3390\/genes16090992","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]}}}