Analysis of genetic variants and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia
10.3760/cma.j.cn511374-20230515-00286
- VernacularTitle:多发性骨骺发育不良一个家系的基因变异鉴定与致病机制分析
- Author:
Shan LI
1
;
Yueyang SHENG
;
Xinyu WANG
;
Ying WANG
;
Yanzhuo ZHANG
;
Cheng′ai WU
;
Xu JIANG
Author Information
1. 首都医科大学附属北京积水潭医院北京市创伤骨科研究所分子骨科，北京 100035
- Keywords:
Multiple epiphyseal dysplasia;
SLC26A2 gene;
Genetic variant;
Pathogenic mechanism
- From:
Chinese Journal of Medical Genetics
2024;41(7):807-811
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the genetic variant and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia (MED).Methods:A MED pedigree which had presented at the Beijing Jishuitan Hospital Affiliated to Capital Medical University on September 13, 2020 was selected as the study subject. Clinical data of the pedigree were collected. Peripheral blood samples were drawn from pedigree members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variant was verified by Sanger sequencing. Wild type and mutant SLC26A2 expression plasmids were constructed and transfected into human primary chondrocytes. The effect of the variants on the protein localization and cell proliferation was determined by immunofluorescence and CCK8 assays. Results:WES and Sanger sequencing revealed that the proband has harbored compound heterozygous variants of the SLC26A2 gene, including a paternally derived c. 484G>T (p.Val162Leu) missense variant and a maternally derived c. 485_486delTG (p.Val162Glyfs*12) frameshifting variant. The SLC26A2 WT and its mutant SLC26A2 Val162Leu and SLC26A2 Val162Glyfs*12 expression plasmids were distributed in the nuclei and cytoplasm of human primary chondrocytes. Compared with SLC26A2 WT, the expressions of SLC26A2 Val162Leu and SLC26A2 Val162Glyfs*12 were decreased, along with reduced proliferation of human primary chondrocytes. Conclusion:The c. 484G>T and c. 485_486delTG compound heterozygous variants of the SLC26A2 gene may affect the proliferation of human primary chondrocytes and underlay the pathogenesis of MED in this pedigree.
