Pjvk, also known as DFNB59, encodes the pejvakin protein. Pejvakin is involved in generating auditory and neural signals in the inner ear [4]. Mutations in Pjvk are associated with autosomal recessive non-syndromic hearing impairment (AR-NSHI) and auditory neuropathy spectrum disorder (ANSD) [1].

Pathogenic variants in Pjvk cause the DFNB59 type of AR-NSHI, with phenotypes ranging from cochlear hearing loss to ANSD [1]. The numbers of reported cases and pathogenic variants are still small for accurate genotype-phenotype correlations [1]. In a study of Spanish familial AR-NSHI and simplex ANSD cases, four novel pathogenic variants were reported, expanding the spectrum of Pjvk mutations [1]. In Pjvk-mutant mice, gene therapy with the synthetic adeno-associated viral vector Anc80L65 restored spiral ganglion neuron density, hair cells in the cochlea, and vestibular ganglion neurons, improving sensorineural hearing impairment and balance function [2]. A transgenic mouse model carrying the c.874G > A (p.G292R) variant was generated to investigate the auditory and vestibular phenotypes of DFNB59 [3].

In conclusion, Pjvk plays a crucial role in auditory and neural signal generation in the inner ear. Mouse models, especially those with Pjvk mutations, have provided insights into the pathophysiology of Pjvk-related hearing impairments, highlighting the potential of gene therapy for treating these inner ear deficits [2].

References:

1. Domínguez-Ruiz, María, Rodríguez-Ballesteros, Montserrat, Gandía, Marta, Santarelli, Rosamaria, Del Castillo, Ignacio. 2022. Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder. In Genes, 13, . doi:10.3390/genes13010149. https://pubmed.ncbi.nlm.nih.gov/35052489/

2. Lu, Ying-Chang, Tsai, Yi-Hsiu, Chan, Yen-Huei, Wu, Chen-Chi, Cheng, Yen-Fu. 2022. Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice. In JCI insight, 7, . doi:10.1172/jci.insight.152941. https://pubmed.ncbi.nlm.nih.gov/36278489/

3. Cheng, Yen-Fu, Tsai, Yi-Hsiu, Huang, Chun-Ying, Hsu, Chuan-Jen, Wu, Chen-Chi. 2020. Generation and pathological characterization of a transgenic mouse model carrying a missense PJVK mutation. In Biochemical and biophysical research communications, 532, 675-681. doi:10.1016/j.bbrc.2020.07.101. https://pubmed.ncbi.nlm.nih.gov/32917362/

4. Mujtaba, Ghulam, Bukhari, Ihtisham, Fatima, Amara, Naz, Sadaf. 2012. A p.C343S missense mutation in PJVK causes progressive hearing loss. In Gene, 504, 98-101. doi:10.1016/j.gene.2012.05.013. https://pubmed.ncbi.nlm.nih.gov/22617256/