Abstract：
The significant variability in the clinical manifestations of COL2A1-associated skeletal dysplasias makes it necessary to conduct a clinical and genetic analysis of individual nosological variants, which will contribute to improving our understanding of the pathogenetic mechanisms and prognosis. We presented the clinical and genetic characteristics of 60 Russian pediatric patients with type II collagenopathies caused by previously described and newly identified variants in the COL2A1 gene. Diagnosis confirmation was carried out by new generation sequencing of the target panel with subsequent validation of the identified variants using automated Sanger sequencing. It has been shown that clinical forms of spondyloepiphyseal dysplasias predominate in childhood, both with more severe clinical manifestations (58%) and with unusual phenotypes of mild forms with normal growth (25%). However, Stickler syndrome, type I was less common (17%). In the COL2A1 gene, 28 novel variants were identified, and a total of 63% of the variants were found in the triple helix region resulted in glycine substitution in Gly-XY repeats, which were identified in patients with clinical manifestations of congenital spondyloepiphyseal dysplasia with varying severity, and were not found in Stickler syndrome, type I and Kniest dysplasia. In the C-propeptide region, five novel variants leading to the development of unusual phenotypes of spondyloepiphyseal dysplasia have been identified.
摘要：
COL2A1相关骨骼发育不良临床表现的显着变异性使得有必要对单个疾病变异进行临床和遗传分析。这将有助于提高我们对发病机制和预后的理解。我们介绍了60名俄罗斯儿科II型胶原病患者的临床和遗传特征，这些患者是由先前描述的和新鉴定的COL2A1基因变体引起的。通过靶组的新一代测序进行诊断确认,随后使用自动化Sanger测序验证所鉴定的变体。研究表明，脊椎骨phy发育不良的临床形式在儿童时期占主导地位，两者均具有更严重的临床表现（58％）和异常的轻度形式和正常生长（25％）。然而,Stickler综合征,I型较不常见(17%)。在COL2A1基因中,确定了28个新的变体，并且在三螺旋区域中发现总共63％的变体导致Gly-XY重复序列中的甘氨酸取代，在临床表现不同严重程度的先天性脊柱骨骨发育不良的患者中，并没有发现Stickler综合征,I型和Kniest发育不良。在C-前肽区,已发现五种新的变异导致脊柱骨骨发育不良异常表型的发展。
