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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- 陆军军医大学学报 2023年45卷第8期 页码：842-846
- 作者机构：
1.400038 重庆，陆军军医大学(第三军医大学)基础医学院医学遗传学教研室
2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院妇产科
- 作者简介：
[郭洪，E-mail: guohong02@gmail.comGUO Hong, E-mail: guohong02@gmail.com
- 基金信息：国家自然科学基金面上项目(82171840);重庆市自然科学基金(cstc2021jcyj-msxmX0281)
DOI：10.16016/j.2097-0927.202209308
中图分类号： R394.1;R596.1;R681.1收稿：2022-09-30，
修回：2022-11-09，
纸质出版：2023-04-30
- 稿件说明：
移动端阅览
李百青, 朱芯潼, 郭洪.
COL10A1 基因新突变导致Schmid型干骺端软骨发育不全[J]. 陆军军医大学学报, 2023,45(8):842-846.Baiqing LI, Xintong ZHU, Hong GUO. A novel mutation in
COL10A1 gene causes Schmid type metaphyseal achondroplasia[J]. Journal of Army Medical University, 2023, 45(8): 842-846.李百青, 朱芯潼, 郭洪.
COL10A1 基因新突变导致Schmid型干骺端软骨发育不全[J]. 陆军军医大学学报, 2023,45(8):842-846. DOI： 10.16016/j.2097-0927.202209308.Baiqing LI, Xintong ZHU, Hong GUO. A novel mutation in
COL10A1 gene causes Schmid type metaphyseal achondroplasia[J]. Journal of Army Medical University, 2023, 45(8): 842-846. DOI： 10.16016/j.2097-0927.202209308.
摘要
目的
2
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
2
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
2
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
2
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。
Abstract
Objective
2
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
2
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
2
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 mo
lecules
and then cause the disease.
Conclusion
2
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.
关键词
Keywords
references
MÄKITIE O, SUSIC M, COLE W G. Early-onset metaphyseal chondrodysplasia type Schmid associated with a COL10A1 frame-shift mutation and impaired trimerization of wild-type α1(X) protein chains[J]. J Orthop Res, 2010, 28(11): 1497-1501. DOI: 10.1002/jor.21161.
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