{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPejvakin, the 352–amino acid protein encoded by the DFNB59/PJVK gene, is predominantly expressed in the cell bodies of neurons along the afferent auditory pathway. Early studies demonstrated that pathogenic missense, nonsense, and frameshift mutations in DFNB59 disrupt normal auditory signal transmission, resulting in abnormal auditory brainstem responses and a neuronal defect underlying nonsyndromic deafness and auditory neuropathy spectrum disorders. These findings, derived from human genetic analyses and transgenic mouse models, established a critical role for pejvakin in the proper neural processing of sound."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSubsequent investigations have expanded our understanding of pejvakin’s function beyond its neuronal localization. Functional studies have revealed that pejvakin associates with peroxisomes and is required for their proliferation in response to oxidative stress—a process that protects auditory hair cells and primary neurons against noise‐induced damage. In parallel, a growing body of genetic research across diverse populations—including cohorts from Iran, Israel, Pakistan, China, and others—has shown that mutations in PJVK result in a broad spectrum of hearing impairment phenotypes. These range from auditory neuropathy to cochlear hearing loss and are associated with clinical challenges such as poor cochlear implant outcomes, underscoring the gene’s clinical diagnostic value. Together, these findings highlight pejvakin as a key mediator of both neuronal function and cellular stress responses in the auditory system."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sedigheh Delmaghani, Francisco J del Castillo, Vincent Michel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1829"}], "href": "https://doi.org/10.1038/ng1829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16804542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16804542"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Inga Ebermann, Martin Walger, Hendrik P N Scholl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Truncating mutation of the DFNB59 gene causes cochlear hearing impairment and central vestibular dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20478"}], "href": "https://doi.org/10.1002/humu.20478"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17301963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17301963"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rob W J Collin, Ersan Kalay, Jaap Oostrik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of DFNB59 mutations in autosomal recessive nonsyndromic hearing impairment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20510"}], "href": "https://doi.org/10.1002/humu.20510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17373699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17373699"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shuai Xu, Zhibin Chen, Yajie Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Sequence analysis of DFNB59 gene in a Chinese family with dominantly inherited auditory neuropathy]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19160860"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19160860"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nejat Mahdieh, Bahareh Rabbani, Susan Wiley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2010.96"}], "href": "https://doi.org/10.1038/jhg.2010.96"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20739942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20739942"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "G Borck, L Rainshtein, S Hellman-Aharony, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High frequency of autosomal-recessive DFNB59 hearing loss in an isolated Arab population in Israel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2011.01741.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2011.01741.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21696384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21696384"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jian Wang, Ying-ying Fan, Shu-juan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants of OTOF and PJVK genes in Chinese patients with auditory neuropathy spectrum disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0024000"}], "href": "https://doi.org/10.1371/journal.pone.0024000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21935370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21935370"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ghulam Mujtaba, Ihtisham Bukhari, Amara Fatima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A p.C343S missense mutation in PJVK causes progressive hearing loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.05.013"}], "href": "https://doi.org/10.1016/j.gene.2012.05.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22617256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22617256"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Qiu-Jing Zhang, Lan Lan, Na Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel mutation of PJVK in the Chinese non-syndromic hearing loss population with low prevalence of the PJVK mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Otolaryngol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/00016489.2014.985799"}], "href": "https://doi.org/10.3109/00016489.2014.985799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25631766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25631766"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chen-Chi Wu, Yin-Hung Lin, Tien-Chen Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identifying Children With Poor Cochlear Implantation Outcomes Using Massively Parallel Sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000001073"}], "href": "https://doi.org/10.1097/MD.0000000000001073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26166082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26166082"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sedigheh Delmaghani, Jean Defourny, Asadollah Aghaie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.10.023"}], "href": "https://doi.org/10.1016/j.cell.2015.10.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26544938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26544938"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "María Domínguez-Ruiz, Montserrat Rodríguez-Ballesteros, Marta Gandía, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Pathogenic Variants in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PJVK"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes13010149"}], "href": "https://doi.org/10.3390/genes13010149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35052489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35052489"}]}]}]}