ORIGINAL RESEARCH article
Front. Genet.
Sec. Statistical Genetics and Methodology
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1654336
This article is part of the Research TopicFunctional Study of Novel VUS (Variant of Uncertain Significance) Mutations in Single-gene Inherited Disease, Volume IIView all 5 articles
Unraveling the Pathogenicity Role of the Novel Compound Heterozygous Mutations of MED25 Gene in a Chinese Patient with BVSYS
Provisionally accepted
- 1Hefei Maternal and Child Health Hospital Reproductive Medicine Center, Hefei, China
- 2Monash University Faculty of Medicine Nursing and Health Sciences, Melbourne, Australia
- 3Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
- 4Jingchu University of Technology, Jingmen, China
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Mediator of RNA polymerase II transcription subunit 25 (MED25), a crucial component of the transcriptional coactivator complex, plays a significant role in the transcription of most RNA polymerase II-dependent genes. Mutations in MED25 have been linked to various genetic syndromes, including Basel-Vanagaite-Smirin-Yosef Syndrome (BVSYS) and Intellectual Disability (ID). Using whole exome sequencing (WES), we identified novel compound heterozygous mutations, c.670C>G (p.R224G) and c.1965+1dup, in the MED25 gene (NM_030973.4) of a proband exhibiting clinical manifestations such as cognitive impairment, language difficulties, intellectual disability, and microcephaly. Through bioinformatics analysis and both in vivo and in vitro gene-splicing assays, we identified that the mutation site c.1965+1dup could affect the splicing of the MED25 gene, while the mutation c.670C>G (p.R224G) could not. However, bioinformatics analysis suggested that the mutation c.670C>G (p.R224G) may affect gene function by altering the structure of the MED25 protein. These findings demonstrate that two mutation sites identified in the MED25 gene in this case are pathogenic or likely pathogenic and may be associated with the clinical phenotype of the proband in this study.
Keywords: MED25, Whole exome sequencing (WES), Compound heterozygous mutation, c.1965+1dup, c.670C>G (p.R224G), gene splicing assay
Received: 26 Jun 2025; Accepted: 05 Aug 2025.
Copyright: © 2025 Zou, Qiu, Dai, Li, Liao and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yulei Li, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
Yan Zhou, Jingchu University of Technology, Jingmen, China
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