{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:44:42Z","timestamp":1788583482628,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union (NextGenerationEU)","award":["BG-RRP-2.004-0009-C02"],"award-info":[{"award-number":["BG-RRP-2.004-0009-C02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Next-generation sequencing (NGS), particularly whole-exome sequencing (WES), has become a powerful diagnostic tool for rare genetic conditions. However, its success rate varies based on the underlying genetic etiology and the population studied. Methods: This retrospective study evaluated the diagnostic yield of NGS in a cohort of 137 pediatric patients with suspected rare genetic disorders in Bulgaria, a setting where such testing is not reimbursed and must be self-funded. The patients underwent either WES or targeted gene panel testing based on clinical presentation, family history, and genetic evaluation. Results: The overall diagnostic yield was 45.99%, with WES achieving 51.25% and targeted testing achieving 38.60%. The highest yield was observed in patients presenting with both dysmorphic features and neurodevelopmental delays (62.5%), while the lowest was observed among those with isolated neurodevelopmental issues (10%). A significant portion of the identified variants (35.9%) were novel. Eight patients were diagnosed with copy number variants (CNVs) detected only through WES. Conclusions: Our findings illustrate the value of WES as a first-line test and highlight the impact of deep phenotyping on diagnostic success. This study also emphasizes the need for a population-specific reference genome and equal access to genomic diagnostics in all European countries.<\/jats:p>","DOI":"10.3390\/medsci13020075","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:11:49Z","timestamp":1749532309000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Diagnostic Yield of Next-Generation Sequencing for Rare Pediatric Genetic Disorders: A Single-Center Experience"],"prefix":"10.3390","volume":"13","author":[{"given":"Milena","family":"Stoyanova","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Medical University Varna, Marin Drinov Str 55, 9000 Varna, Bulgaria"},{"name":"Laboratory of Medical Genetics, St. Marina Hospital, Hristo Smirnenski Blv 1, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3410-5033","authenticated-orcid":false,"given":"Dinnar","family":"Yahya","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University Varna, Marin Drinov Str 55, 9000 Varna, Bulgaria"},{"name":"Laboratory of Medical Genetics, St. Marina Hospital, Hristo Smirnenski Blv 1, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8847-4651","authenticated-orcid":false,"given":"Mari","family":"Hachmeriyan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University Varna, Marin Drinov Str 55, 9000 Varna, Bulgaria"},{"name":"Laboratory of Medical Genetics, St. Marina Hospital, Hristo Smirnenski Blv 1, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-7263","authenticated-orcid":false,"given":"Mariya","family":"Levkova","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University Varna, Marin Drinov Str 55, 9000 Varna, Bulgaria"},{"name":"Laboratory of Medical Genetics, St. Marina Hospital, Hristo Smirnenski Blv 1, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41431-019-0508-0","article-title":"Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database","volume":"28","author":"Lambert","year":"2020","journal-title":"Eur. 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