Abstract
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.