A novel missense COL10A1 mutation: c.2020G>A; p. Gly674Arg linked with the bowed legs stature in the Schmid metaphyseal chondrodysplasia-affected Chinese lineage

Qiong Chen; Sheng-Nan Wu; Yong-Xing Chen; Selvaa Kumar C; Lu Zhang; Hai-Yan Wei; Senthil Arun Kumar

doi:10.1016/j.bonr.2019.100240

A novel missense COL10A1 mutation: c.2020G>A; p. Gly674Arg linked with the bowed legs stature in the Schmid metaphyseal chondrodysplasia-affected Chinese lineage

Bone Rep. 2019 Dec 13:12:100240. doi: 10.1016/j.bonr.2019.100240. eCollection 2020 Jun.

Authors

Qiong Chen¹, Sheng-Nan Wu¹, Yong-Xing Chen¹, Selvaa Kumar C², Lu Zhang³, Hai-Yan Wei¹, Senthil Arun Kumar¹

Affiliations

¹ 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.
² School of Biotechnology and Bioinformatics, D. Y. Patil Deemed to be University, Sector-15, CBD Belapur, Navi Mumbai 400614, India.
³ Shanghai We-Health Biomedical Technology Co. Ltd, Shanghai 201315, China.

Abstract

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.

Keywords: Bowed legs; COL10A1 mutation; Early diagnosis; Mutant α1(X) chain; Schmid metaphyseal chondrodysplasia; Ulna bone.

Publication types

Case Reports