Stoyanova Milena, Yahya Dinnar, Hachmeriyan Mari, Levkova Mariya
Department of Medical Genetics, Medical University Varna, Marin Drinov Str 55, 9000 Varna, Bulgaria.
Laboratory of Medical Genetics, St. Marina Hospital, Hristo Smirnenski Blv 1, 9000 Varna, Bulgaria.
Med Sci (Basel). 2025 Jun 9;13(2):75. doi: 10.3390/medsci13020075.
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. : 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. : 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. : 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.
下一代测序（NGS），尤其是全外显子组测序（WES），已成为诊断罕见遗传病的强大工具。然而，其成功率因潜在的遗传病因和所研究的人群而异。：这项回顾性研究评估了在保加利亚137例疑似罕见遗传病患儿中NGS的诊断率，在该国这种检测不报销，必须自费。根据临床表现、家族史和基因评估，患者接受了WES或靶向基因panel检测。：总体诊断率为45.99%，WES为51.25%，靶向检测为38.60%。在既有畸形特征又有神经发育迟缓的患者中诊断率最高（62.5%），而在仅有神经发育问题的患者中最低（10%）。很大一部分已鉴定的变异（35.9%）是新发现的。8例患者被诊断出仅通过WES检测到的拷贝数变异（CNV）。：我们的研究结果说明了WES作为一线检测的价值，并突出了深度表型分析对诊断成功的影响。这项研究还强调了在所有欧洲国家需要有针对特定人群的参考基因组以及平等获得基因组诊断的机会。
