ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1641999
A Novel Deletion Upstream of POU3F4 in a Chinese Family with X-linked deafness 2 and a Literature Review
Provisionally accepted
- 1West China Second University Hospital, Sichuan University, Chengdu, China
- 2Guizhou Provincial People's Hospital, Guiyang, China
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Abstract Background： X-linked deafness 2 (DFNX2) is a rare hereditary hearing loss characterized by progressive conductive and sensorineural hearing loss and a pathognomonic temporal bone deformity. DFNX2 is caused by mutations in the coding sequence or deletions upstream of POU3F4. Only 12 upstream deletions of POU3F4 associated with DFNX2 have been reported, and the precise mechanisms underlying its pathogenesis remain fully elucidated. Methods： Whole-genome Sequencing (WGS) and linkage analysis were performed to identify potential genetic etiologies. Gap-PCR and Sanger sequencing were used to validate candidate pathogenic variants and elucidate the breakpoints. Quantitative Polymerase Chain Reaction (qPCR) was conducted to evaluate the altered expression of both POU3F4 and its downstream target genes. Results: Here, we identified a novel deletion approximately 795.5 kb in length, located about 140 kb upstream of POU3F4 in a large Chinese family. All patients are hemizygous for this deletion, and the breakpoints have been confirmed to be located at GRCh37(chrX): g.81840743_82636209. Additionally, qPCR analysis demonstrated a significant reduction in the expression levels of both POU3F4 and its downstream target genes in the affected patients, which had not been reported in previous studies. We expand the spectrum of pathogenic deletions upstream of POU3F4 associated with DFNX2. Conclusions: This study provides new molecular evidence that deletions upstream of POU3F4 can disrupt the expression of POU3F4 and its downstream target genes in humans. Our results also enhance the understanding of the pathogenic mechanisms underlying DFNX2 associated with these deletions, as well as the downstream gene networks of POU3F4.
Keywords: Deletions upstream of POU3F4, X-linked deafness 2, POU3F4 gene, Whole-genome sequencing, Hearing Loss
Received: 05 Jun 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Yang, Huang, Liu, Mu, Bai, Jing, Xing and Liu. 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: Hongqian Liu, liuhongqian@scu.edu.cn
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