PTPRQ, the protein tyrosine phosphatase receptor Q, is a member of the type III tyrosine phosphatase receptor (R3 PTPR) family. It has phosphotyrosine phosphatase and phosphatidylinositol phosphatase activities, regulating cell proliferation, apoptosis, differentiation, and survival. PTPRQ is essential for the normal maturation and function of hair bundle in the cochlea [2].

PTPRQ-associated hearing loss (HL) is a significant finding. In a study of 15,684 patients with sensorineural hearing loss (SNHL), 17 possibly disease-causing PTPRQ variants were identified in 13 Japanese patients, with 15 of them novel. Most variants were loss-of-function. Patients mostly had congenital or childhood onset, with high-frequency hearing deteriorating earlier. The severity progressed from moderate to severe or profound HL [1]. A novel PTPRQ truncating pathogenic variant, c.3697del, was identified in a Chinese Han family with autosomal dominant, postlingual, progressive hearing loss. The Ptprq-3700del knock-in mouse model showed that homozygous mice had profound hearing loss at 3 weeks, and heterozygous mice had mild, progressive hearing loss from 3 to 12 weeks, mainly affecting high frequencies, with disorganized stereocilia [4].

In conclusion, PTPRQ is crucial for cochlear hair bundle maturation. Research on PTPRQ-related mouse models has revealed its significant role in hearing loss, especially in understanding the mechanisms of autosomal dominant and recessive non-syndromic hearing loss, providing insights for further functional studies and potential therapeutic strategies [1,3,4].

References:

1. Sakuma, Naoko, Nishio, Shin-Ya, Goto, Shin-Ichi, Okubo, Kimihiro, Usami, Shin-Ichi. 2024. Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort. In Genes, 15, . doi:10.3390/genes15040489. https://pubmed.ncbi.nlm.nih.gov/38674423/

2. Zhang, Wansi, Tang, Zhimin, Fan, Shipan, Deng, Wenxin, Ying, Ying. . Protein Tyrosine Phosphatase Receptor-type Q: Structure, Activity, and Implications in Human Disease. In Protein and peptide letters, 29, 567-573. doi:10.2174/0929866529666220511141826. https://pubmed.ncbi.nlm.nih.gov/35546749/

3. Oziębło, Dominika, Sarosiak, Anna, Leja, Marcin L, Skarżyński, Henryk, Ołdak, Monika. 2019. First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene. In Journal of translational medicine, 17, 351. doi:10.1186/s12967-019-2099-5. https://pubmed.ncbi.nlm.nih.gov/31655630/

4. Zhou, Yaqi, Yin, Na, Ji, Lingchao, Hu, Hongyi, Mei, Xueshuang. 2024. A Novel PTPRQ c.3697del Variant Causes Autosomal Dominant Progressive Hearing Loss in Both Humans and Mice. In Clinical genetics, 107, 208-213. doi:10.1111/cge.14634. https://pubmed.ncbi.nlm.nih.gov/39434500/