Exploration of the pathogenic mechanism of a novel c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene
10.3760/cma.j.cn511374-20250218-00085
- VernacularTitle:SOX10基因c.661_664dup(p.P222Lfs*60)新发变异致病机理的探讨
- Author:
Huiying LI
1
;
Peipei CHEN
1
;
Pingping LIU
1
;
Shanshan YU
1
;
Xiaodan JIN
1
;
Shuang ZHAO
1
Author Information
1. 邯郸市第一医院胎儿医学科遗传与产前诊断室，邯郸 130400
- Publication Type:Journal Article
- Keywords:
SOX10 gene;
Whole exome sequencing;
In vitro experiment
- From:
Chinese Journal of Medical Genetics
2025;42(5):574-578
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. Methods:A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c. 661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 μg/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committe of Handan First Hospital(Ethics No.HDYY-LW-25053). Results:The child was found to harbor a heterozygous c. 661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. Conclusion:The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.
