RT Journal Article SR Electronic T1 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2017-104954 DO 10.1136/jmedgenet-2017-104954 A1 Xue Gao A1 Yong-Yi Yuan A1 Qiong-Fen Lin A1 Jin-Cao Xu A1 Wei-Qian Wang A1 Yue-Hua Qiao A1 Dong-Yang Kang A1 Dan Bai A1 Feng Xin A1 Sha-Sha Huang A1 Shi-Wei Qiu A1 Li-Ping Guan A1 Yu Su A1 Guo-Jian Wang A1 Ming-Yu Han A1 Yi Jiang A1 Han-Kui Liu A1 Pu Dai YR 2018 UL http://jmg.bmj.com/content/early/2018/02/16/jmedgenet-2017-104954.abstract AB Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder.Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL).Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism.Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL. Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level.Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.