Abstract
Objectives
This study aimed to identify the causative variants in a patient with Waardenburg syndrome (WS) type 2 using whole exome sequencing (WES).
Methods
The clinical features of the patient were collected. WES was performed on the patient and his parents to screen causative genetic variants and Sanger sequencing was performed to validate the candidate mutation. The AlphaFold2 software was used to predict the changes in the 3D structure of the mutant protein. Western blotting and immunocytochemistry were used to determine the SOX10 mutant in vitro.
Results
A de novo variant of SOX10 gene, NM_006941.4: c.707_714del (p. H236Pfs*42), was identified, and it was predicted to disrupt the wild-type DIM/HMG conformation in SOX10. In-vitro analysis showed an increased level of expression of the mutant compared to the wild-type.
Conclusions
Our findings helped to understand the genotype-phenotype association in WS2 cases with SOX10 mutations.
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Data availability
No datasets were generated or analysed during the current study.
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Funding
This work was supported by the National Natural Science Foundation of China (Grant Number: 81901325); Guangxi Medicine and Health Science Research Project (Grant Number: Z20170988); Guangxi Medical University Youth Science Foundation (Grant Number: GXMUYSF201804); Scientific Research and Technology Development Program of Wuzhou (Grant Number: 2021F01439).
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ZL and KX wrote the manuscript text; ZZ and CL prepared Figs. 1, 2 and 3; WG and JR prepared Table 1.
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Li, Z., Xu, K., Zhou, Z. et al. A novel SOX10 mutation causing Waardenburg syndrome type 2 by expressing a truncated and dysfunctional protein in a Chinese child. Mol Biol Rep 51, 536 (2024). https://doi.org/10.1007/s11033-024-09469-7
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DOI: https://doi.org/10.1007/s11033-024-09469-7