Abstract：
Pathogenic single nucleotide variants (SNVs) found in the COL2A1 gene are associated with a broad range of skeletal dysplasias due to their impact on the structure and function of the Col2a1 protein. However, the molecular mechanisms of some nucleotide variants detected during diagnostic testing remain unclear. The interpretation of missense and splicing variants caused by SNVs poses a significant challenge for clinicians. In this work, we analyzed 22 splicing variants in the COL2A1 gene which have been found in patients with COL2A1-associated skeletal dysplasias. Using a minigene system, we investigated the impact of these SNVs on splicing and gained insights into their molecular mechanisms and genotype-phenotype correlations for each patient. The results of our study are very useful for improving the accuracy of diagnosis and the management of patients with skeletal dysplasias caused by SNVs in the COL2A1 gene.
摘要：
在COL2A1基因中发现的致病性单核苷酸变体（SNV）与广泛的骨骼发育不良有关，因为它们对Col2a1蛋白的结构和功能有影响。然而,在诊断性检测中检测到的某些核苷酸变异的分子机制尚不清楚.由SNV引起的错义和剪接变体的解释对临床医生提出了重大挑战。在这项工作中,我们分析了COL2A1基因的22个剪接变异,这些变异在COL2A1相关骨骼发育不良患者中发现.使用小基因系统，我们研究了这些SNV对剪接的影响,并深入了解了每个患者的分子机制和基因型-表型相关性.我们的研究结果对于提高诊断的准确性和COL2A1基因中SNV引起的骨骼发育不良患者的治疗非常有用。
