| First Author | Yariz KO | Year | 2012 |
| Journal | Am J Hum Genet | Volume | 91 |
| Issue | 5 | Pages | 872-82 |
| PubMed ID | 23122586 | Mgi Jnum | J:203658 |
| Mgi Id | MGI:5528437 | Doi | 10.1016/j.ajhg.2012.09.011 |
| Citation | Yariz KO, et al. (2012) Mutations in OTOGL, encoding the inner ear protein otogelin-like, cause moderate sensorineural hearing loss. Am J Hum Genet 91(5):872-82 |
| abstractText | Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs( *)25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg183( *)) and c.5238+5G>A, in a nonconsanguineous family with moderate nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at 12q21.31 and encodes otogelin-like, which has structural similarities to the epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed in the inner ear of vertebrates with a transcription level that is high in embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is localized to the acellular membranes of the cochlea and the vestibular system and to a variety of inner ear cells located underneath these membranes. Knocking down of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and anatomical changes in the inner ear, supporting that otogelin-like is essential for normal inner ear function. We propose that OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss. |
