Clinical Characteristics of Hearing Loss Caused by P2RX2 Gene Variants
Shogo Oyamada, Shin-ya Nishio, Takechiyo Yamada, Hiroshi Nakanishi, Kiyoshi Oda, Yohei Honkura, Masaomi Motegi, Taku Ito, Naoko Sakuma, Kozo Kumakawa, Marina Kobayashi, Hiroko Monobe, Yasuhiro Arai, Hidekane Yoshimura, Jun Nakayama, Takashi Nakamura, Akitoshi Mitani, Chihiro Morimoto, Shin-ichi UsamiBackground/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.