A novel mutation in <italic style="font-style: italic">COL10A1</italic> gene causes Schmid type metaphyseal achondroplasia

Baiqing LI; Xintong ZHU; Hong GUO

doi:10.16016/j.2097-0927.202209308

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A novel mutation in COL10A1 gene causes Schmid type metaphyseal achondroplasia

Clinical Medicine | 更新时间：2026-01-09

- A novel mutation in COL10A1 gene causes Schmid type metaphyseal achondroplasia
- Journal of Army Medical University Vol. 45, Issue 8, Pages: 842-846(2023)
- 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：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82171840);the Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0281)
- DOI：10.16016/j.2097-0927.202209308
  CLC： R394.1;R596.1;R681.1
- Received：30 September 2022，
  
  Revised：2022-11-09，
  
  Published：30 April 2023
- 稿件说明：
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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：

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

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。

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 mo

lecules

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.

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.

GOYAL M, GUPTA A, CHOUDHARY A, et al . Schmid type metaphyseal chondrodysplasia with a novel COL10A1 mutation[J ] . Indian J Pediatr, 2019, 86(2): 183-185. DOI: 10.1007/s12098-018-2791-0.

ZHU Y, LI L, ZHOU L, et al . A novel mutation leading to elongation of the deduced α1(X) chain results in Metaphyseal Chondrodysplasia type Schmid[J ] . Clin Chim Acta, 2011, 412(13/14): 1266-1269. DOI: 10.1016/j.cca.2011.03.026.

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WU H, WANG S, LI G, et al . Characterization of a novel COL10A1 variant associated with Schmid-type metaphyseal chondrodysplasia and a literature review[J ] . Mol Genet Genomic Med, 2021, 9(5): e1668. DOI: 10.1002/mgg3.1668.

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A novel mutation in COL10A1 gene causes Schmid type metaphyseal achondroplasia

DOI：10.16016/j.2097-0927.202209308

摘要

Abstract

关键词

Keywords

references