Chen Qiong, Wu Sheng-Nan, Chen Yong-Xing, C Selvaa Kumar, Zhang Lu, Wei Hai-Yan, Kumar Senthil Arun
Department of Endocrinology and Metabolism, Henan provincial key laboratory of children's genetics and metabolic diseases, Henan children's hospital (Children's hospital affiliated to Zhengzhou University), No-33, Longhu Waihuan East road, Zhengzhou 450018, China.
School of Biotechnology and Bioinformatics, D. Y. Patil Deemed to be University, Sector-15, CBD Belapur, Navi Mumbai 400614, India.
Bone Rep. 2019 Dec 13;12:100240. doi: 10.1016/j.bonr.2019.100240. eCollection 2020 Jun.
To evaluate the clinical-phenotypic characteristics of Schmid metaphyseal chondrodysplasia (SMCD) inflicted by a novel missense mutation of COL10A1 gene: c.2020G > A; p.Gly674Arg. A female child aged about 3 yrs. and 8 months was subjected to Radiograph test to validate the symptoms of SMCD. The polymorphism analysis by the next-generation sequencing (NGS) was performed using the peripheral blood DNA samples of the patient and other family inmates, including, the younger male sibling. The effect of the mutation on the non-collagenous carboxyl-terminal (NC1) domain of collagen X was studied using the SWISS-MODEL online server for trimer modelling; PROSA and PROCHECK-Ramachandran plot for structural validation; Mean Square Plot (RMSF) for structural rigidity. Radiograph examination of lower limbs confirmed the bowed legs in both the patient and her younger brother (study groups). The inheritance of the novel missense mutation of COL10A1: c.2020G > A; p.Gly674Arg (at chromosome-6q22.1) was confirmed in the study groups from the SMCD-affected mother. The extended interactions of the mutant-Arg674 with the Ser552 and Phe589 (β strand B) in the NC1 domain of α1(X) chain monomer is more likely to intervene its trimer formation by weakening the structural rigidity of the crucial strand H compared to its wild type. This plausibly deters the collagen X synthesis inflicting the bowed legs with the altered distal ulna bone morphology in the study groups. The inheritance of COL10A1 mutation: c.2020G > A; p.Gly674Arg has inflicted the SMCD with the characteristic bowed legs in the study groups. Radiograph and NGS could be a valid diagnostic module to initiate the treatment of SMCD.
为评估由COL10A1基因新型错义突变：c.2020G>A；p.Gly674Arg导致的施密德干骺端软骨发育不良（SMCD）的临床表型特征。一名约3岁8个月的女童接受了X线检查以验证SMCD的症状。使用患者及其包括弟弟在内的其他家庭成员的外周血DNA样本，通过下一代测序（NGS）进行多态性分析。使用SWISS-MODEL在线服务器进行三聚体建模，研究该突变对胶原蛋白X非胶原羧基末端（NC1）结构域的影响；使用PROSA和PROCHECK-Ramachandran图进行结构验证；使用均方图（RMSF）进行结构刚性分析。下肢X线检查证实患者及其弟弟（研究组）均有弓形腿。在受SMCD影响的母亲的研究组中，证实了COL10A1基因新型错义突变：c.2020G>A；p.Gly674Arg（位于6号染色体q22.1）的遗传情况。与野生型相比，突变型Arg674与α1(X)链单体NC1结构域中的Ser552和Phe589（β链B）的扩展相互作用更有可能通过削弱关键链H的结构刚性来干预其三聚体形成。这可能阻止了胶原蛋白X的合成，导致研究组出现弓形腿和尺骨远端骨形态改变。COL10A1突变：c.2020G>A；p.Gly674Arg的遗传导致研究组出现具有特征性弓形腿的SMCD。X线检查和NGS可能是启动SMCD治疗的有效诊断模块。
