Clinical Characteristics of Hearing Loss Caused by P2RX2 Gene Variants
Background/Objectives: The P2RX2 gene encoding an ATP-gated ion channel purinoreceptor is a genetic cause of autosomal dominant non-syndromic hearing loss (DFNA41). P2RX2 is a rare causative gene and its detailed clinical characteristics remain unclear. Methods: In this study, we performed next-generation DNA sequencing analysis covering 158 genes previously reported to be associated with non-syndromic and syndromic hearing loss in 18,475 patients. Results: We identified 29 patients from 22 independent families carrying candidate P2RX2 variants. All of the patients showed late-onset progressive hearing loss. In addition, several cases showed asymmetric hearing deterioration. Among the 29 patients, 23 from 19 unrelated families carried the same c.1057G>A variant, which was identified as a founder mutation by SNP-based haplotype analysis. Conclusions: Our findings indicate that late-onset asymmetric progressive hearing deterioration is a characteristic/unique feature of P2RX2-associated hearing loss, which may be related to noise exposure. Our results may be useful in further clarifying the natural history of and optimizing the management strategies for P2RX2-related hearing loss.
Authors
- Hidekane Yoshimura (ORCID: https://orcid.org/0000-0001-9601-7496)
- Shogo Oyamada (ORCID: https://orcid.org/0000-0002-0053-0736)
- Chihiro Morimoto (ORCID: https://orcid.org/0000-0001-5406-901X)
- Masaomi Motegi (ORCID: https://orcid.org/0000-0003-0947-6526)
- Akitoshi Mitani (ORCID: https://orcid.org/0000-0002-2062-5505)
- Shin‐ya Nishio (ORCID: https://orcid.org/0000-0001-6640-2297)
- Hiroko Monobe
- Hiroshi Nakanishi (ORCID: https://orcid.org/0000-0003-2610-3203)
- Shin‐ichi Usami (ORCID: https://orcid.org/0000-0002-5068-6122)
- Yasuhiro Arai (ORCID: https://orcid.org/0000-0002-3622-4482)
- Taku Ito (ORCID: https://orcid.org/0000-0002-8368-9573)
- Yohei Honkura (ORCID: https://orcid.org/0000-0003-2619-2824)
- Kozo Kumakawa (ORCID: https://orcid.org/0000-0001-5802-7386)
- 佐久間 直子
- Jun Nakayama (ORCID: https://orcid.org/0000-0001-6773-2802)
- Kiyoshi Oda
- Marina Kobayashi
- Takechiyo Yamada
- Takashi Nakamura
Institutions
- Kansai Medical University (JP)
- Hamamatsu University (JP)
- Shinshu University (JP)
- Shiga University of Medical Science (JP)
- Gunma University (JP)
- Iwate Medical University (JP)
- Tohoku University (JP)
- Akita University (JP)
- Hamamatsu University School of Medicine (JP)
- Kyoto Prefectural University of Medicine (JP)
- Japanese Red Cross Medical Center (JP)
- Shinshu University Hospital (JP)
- Tohoku Rosai Hospital (JP)
- Mita Hospital (JP)
- Toranomon Hospital (JP)
- Institute of Science Tokyo (JP)
- Nara Medical University (JP)
- Nippon Medical School (JP)
- Yokohama City University (JP)
Publication Details
- Journal
- Genes
- Published
- 2026-11-05
- DOI
- https://doi.org/10.3390/genes17111397
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 0.00