A novel mutation in COL10A1 gene causes Schmid type metaphyseal achondroplasia

Abstract

Objective Schmid type metaphyseal chondrodysplasia (SMCD) is an autosomal dominant chondrodysplasia characterized by abnormal gait and skeletal deformity of limbs. In the study, we analyzed the phenotype and genotype of SMCD in a family who were admitted the Second Affiliated Hospital of our university in January 2021, and then discussed its prevention and treatment based on literature review. Methods We collected the clinical data of the patient and his family members. Then whole exome sequencing and sanger sequencing were used to identify the gene mutation. Bioinformatics analysis was performed in combination with American College of Medical Genetics (ACMG) guidelines to evaluate the pathogenicity of the variants. Results We discovered a novel heterozygous missense mutation c.1843T>G (p.Tyr615Asp) in COL10A1 gene, which was highly conserved among different species. This mutation might affect the trimerization of type X collagen (α1) protein and its binding to extracellular matrix molecules, and then cause the disease. Conclusion We identify a novel COL10A1 mutation, which not only enriches the mutation spectrum of SMCD in Chinese population, but also provides theoretical basis for its prevention, diagnosis and treatment.

Keywords

• schmid type metaphyseal chondrodysplasia
• col10a1
• endoplasmic reticulum stress
• type x collagen (α1)
• gene diagnosis