多发性骨软骨瘤 (MO) 是一种罕见的常染色体显性骨骼疾病，其特征是形成称为骨软骨瘤的多发性良性肿瘤。这种情况主要是由 EXT1 或 EXT2 基因的功能丧失变异引起的，通过既定的诊断标准有助于相对精确的临床诊断。尽管如此，在对两个基因的编码区进行测序和拷贝数分析后，仍有相当一部分 MO 病例 (10%-20%) 仍未得到解决。在我们的研究中，我们在两名患者中发现了镶嵌结构变异，这两名患者最初在 MO 标准遗传分析中得到了阴性结果。具体来说，检测到影响 EXT1 基因中外显子 8-11 和外显子 2-11 的嵌合缺失。其中一例进行了 RNA 分析，两例均进行了基因组测序。迄今为止，仅报道了与 MO 相关的六种嵌合拷贝数变异，代表这两个基因的已知变异中的少数。我们的报告对这些发现进行了详细分析，强调了先进的基因测试技术在检测 EXT1/2 基因中的嵌合变异方面的重要性。版权所有 © 2024 Borovikov, Marakhonov, Murtazina, Davydenko, Filatova, Galeeva, Kadnikova, Ogorodova, Gorodilova,卡尼维茨、皮扬科夫、热尔戴夫、佩特尔古佐夫、祖布科夫、波利亚科夫、沙吉娜和斯科布洛夫。

Multiple osteochondromas (MO) is a rare autosomal dominant skeletal disorder characterized by the development of multiple benign tumors known as osteochondromas. The condition is predominantly caused by loss-of-function variants in the EXT1 or EXT2 genes, facilitating relatively precise clinical diagnosis through established diagnostic criteria. Despite this, a notable percentage of MO cases (10%-20%) remains unresolved after sequencing coding regions and copy number analysis of both genes. In our study, we identified mosaic structural variants in two patients who initially yielded negative results on standard genetic analysis for MO. Specifically, mosaic deletions affecting exons 8-11 and exons 2-11 in the EXT1 gene were detected. RNA analysis was performed in one case, while both cases underwent genome sequencing. To date, only six mosaic copy number variations have been reported in association with MO, representing a minority among known variants in both genes. Our report provides a detailed analysis of these findings, highlighting the significance of advanced genetic testing techniques in detecting mosaic variants in the EXT1/2 genes.Copyright © 2024 Borovikov, Marakhonov, Murtazina, Davydenko, Filatova, Galeeva, Kadnikova, Ogorodova, Gorodilova, Kanivets, Pyankov, Zherdev, Petel’guzov, Zubkov, Polyakov, Shchagina and Skoblov.