COL10A1基因新突变导致Schmid型干骺端软骨发育不全

A novel mutation in COL10A1 gene causes Schmid type metaphyseal achondroplasia

目的对2021年1月陆军军医大学第二附属医院接诊的1例Schmid型干骺端软骨发育不全(Schmid type metaphyseal chondrodysplasia,SMCD)家系进行疾病表型与基因型分析,结合文献复习探讨其防治手段。方法对先证者进行家系调查及系谱分析,收集先证者及家系成员的临床资料,采用全外显子组测序明确突变基因,并通过Sanger测序验证和家系共分离分析,同时结合ACMG指南进行生物信息学分析来评价变异的致病性。结果在家系患者中发现COL10A1基因存在新的杂合错义突变c.1843T>G(p.Tyr615Asp),该位点所在区域在不同物种之间高度保守,此突变可能通过影响X型胶原(α1)蛋白的三聚化及其与细胞外基质分子结合导致疾病发生。结论发现了1种SMCD的新突变,丰富了SMCD患者的突变谱,为SMCD的预防、诊断及治疗提供理论依据。

ObjectiveSchmid 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.MethodsWe 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.ResultsWe 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.ConclusionWe 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.