Kovanda A, Miljanović O, Lovrečić L, Maver A, Hodžić A, Peterlin B
Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Balkan J Med Genet. 2025 Mar 6;27(2):87-93. doi: 10.2478/bjmg-2024-0021. eCollection 2024 Dec.
Optical genome mapping (OGM) is a novel method enabling the detection of structural genomic variants. The method is based on the laser image acquisition of single, labeled, high-molecular-weight DNA molecules and can detect structural genomic variants such as translocations, inversions, insertions, deletions, duplications, and complex structural rearrangements. We aim to present our experience with OGM at the Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Slovenia. Since its introduction in 2021, we have used OGM for the testing of facioscapulohumeral muscular dystrophy 1, characterization and resolution of variants identified by other technologies such as microarrays, exome and genome next-generation sequencing, karyotyping, as well as testing of rare disease patients in whom no genetic cause could be identified using these methods. We present an example family case of two previously undiagnosed male siblings with an overlapping clinical presentation of thrombocytopenia, obesity, and presacral teratoma. After karyotyping, microarray analysis and next-generation sequencing, by using OGM, a maternally inherited cryptic translocation t(X;18)(q27.1;q12.2) was identified in both brothers. Despite an extended segregation analysis, based on strictly applied ACMG criteria and ClinGen guidelines, the identified translocation remains a variant of unknown significance. Despite the remaining limitations of OGM, which will hopefully be resolved by improvements in databases of known benign SV variation and the establishment of official guidelines on the clinical interpretation of OGM variants, our work highlights the complexity of the diagnostic journey, including this novel method, in rare disease cases.
光学基因组图谱（OGM）是一种能够检测结构基因组变异的新方法。该方法基于对单个、标记的高分子量DNA分子进行激光图像采集，可检测结构基因组变异，如易位、倒位、插入、缺失、重复和复杂的结构重排。我们旨在介绍我们在斯洛文尼亚卢布尔雅那大学医学中心基因组医学临床研究所使用OGM的经验。自2021年引入以来，我们已将OGM用于面肩肱型肌营养不良1型的检测、对通过其他技术（如微阵列、外显子组和基因组下一代测序、核型分析）鉴定的变异进行特征描述和解析，以及对使用这些方法无法确定遗传病因的罕见病患者进行检测。我们展示了一个家族病例，有两名先前未确诊的男性同胞，临床表现为血小板减少、肥胖和骶前畸胎瘤。在进行核型分析、微阵列分析和下一代测序后，通过使用OGM，在两兄弟中均发现了一种母系遗传的隐匿性易位t(X;18)(q27.1;q12.2)。尽管进行了广泛的分离分析，但根据严格应用的ACMG标准和ClinGen指南，所确定的易位仍然是一种意义未明的变异。尽管OGM仍存在局限性，希望通过已知良性SV变异数据库的改进以及OGM变异临床解释官方指南的建立来解决这些问题，但我们的工作突出了罕见病病例诊断过程的复杂性，包括这种新方法。
