Dominika Ozieblo 1,2, A-F
Monika Oldak 1, A-G
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Department of Genetics, Institute of Physiology and Pathology of Hearing, Warsaw, Poland
Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
Department of Otoneurology, Institute of Physiology and Pathology of Hearing, Warsaw, Poland
Oto-Rhino-Laryngology Surgery Clinic, Institute of Physiology and Pathology of Hearing, Warsaw, Poland
A - Research concept and design; B - Collection and/or assembly of data; C - Data analysis and interpretation; D - Writing the article; E - Critical revision of the article; F - Final approval of article;
Publication date: 2018-03-31
Corresponding author
Monika Oldak   

Monika Ołdak, MD, PhD, Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Mokra 17, Kajetany, 05-830 Nadarzyn, Tel.: +48-22-356-03-66; Fax: +48-22-356-03-67; e-mail: m.oldak@ifps.org.pl
J Hear Sci 2018;8(1):31-37
The COCH gene encoding cochlin is highly expressed in the inner ear but the exact physiological function of the protein still remains unknown. Pathogenic variants located in COCH cause autosomal dominant hearing loss with possible vestibular involvement.

Material and Methods:
A five-generation Polish family with autosomal dominant hearing loss and tinnitus was recruited for the study. Audiological and vestibular assessments were conducted and clinical exome sequencing was performed in the index patient. Next, co-segregation of the detected variant with hearing loss in the family was confirmed using Sanger sequencing

All affected individuals presented postlingual, progressive hearing loss mainly affecting high frequencies. No vestibular dysfunction was detected. In this study, we have identified a very rare COCH p.Ile374Thr pathogenic variant that segregated with the disease.

Our study provides an independent confirmation of the pathogenic role of COCH c.1115T>C in hearing loss. In addition to hearing loss, individuals with COCH pathogenic variants may also suffer from tinnitus and vertigo.

Tucci D, Merson MH, Wilson BS. A summary of the literature on global hearing impairment: current status and priorities for action. Otol Neurotol, 2010; 31(1): 31-41.
Dawes P, Platt H, Horan M, Ollier W, Munro K, Pendleton N, et al. No association between apolipoprotein E or N-acetyltransferase 2 gene polymorphisms and age-related hearing loss. Laryngoscope, 2015; 125(1): E33-8.
Jecmenica J, Bajec-Opancina A, Jecmenica D. Genetic hearing impairment. Child’s nervous system. ChNS, 2015; 31(4): 515-9.
Smith RJH, Shearer AE, Hildebrand MS. Deafness and hereditary hearing loss overview. GeneReviews, 1999 [updated 2014 Jan 9]. Available from: http://www.ncbi.nlm.nih.gov/bo....
Vona B, Nanda I, Hofrichter MA, Shehata-Dieler W, Haaf T. Non-syndromic hearing loss gene identification: A brief history and glimpse into the future. Mol Cellular Probes, 2015; 29(5): 260-70.
Robertson NG, Resendes BL, Lin JS, Lee C, Aster JC, Adams JC, et al. Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9. Human Mol Genetics, 2001; 10(22): 2493-500.
Parzefall T, Frohne A, Koenighofer M, Kirchnawy A, Streubel B, Schoefer C, et al. Identification of a rare COCH mutation by whole-exome sequencing: implications for personalized therapeutic rehabilitation in an Austrian family with non-syndromic autosomal dominant late-onset hearing loss. Wien Klin Wochenschr, 2017.
Ikezono T, Omori A, Ichinose S, Pawankar R, Watanabe A, Yagi T. Identification of the protein product of the Coch gene (hereditary deafness gene) as the major component of bovine inner ear protein. Biochimica Biophysica Acta, 2001; 1535(3): 258-65.
Robertson NG, Skvorak AB, Yin Y, Weremowicz S, Johnson KR, Kovatch KA, et al. Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9. Genomics, 1997; 46(3): 345-54.
de Kok YJ, Bom SJ, Brunt TM, Kemperman MH, van Beusekom E, van der Velde-Visser SD, et al. A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects. Human Mol Genetics, 1999; 8(2): 361-6.
Robertson NG, Lu L, Heller S, Merchant SN, Eavey RD, McKenna M, et al. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nature Genetics, 1998; 20(3): 299-303.
Jung J, Kim HS, Lee MG, Yang EJ, Choi JY. Novel COCH p.V123E Mutation, Causative of DFNA9 sensorineural hearing loss and vestibular disorder, shows impaired cochlin posttranslational cleavage and secretion. Human Mutation, 2015; 36(12): 1168-75.
Tsukada K, Ichinose A, Miyagawa M, Mori K, Hattori M, Nishio SY, et al. Detailed hearing and vestibular profiles in the patients with COCH mutations. Annals Otol, Rhinol Laryngol, 2015; 124 Suppl 1: 100S-110S.
Recommended procedure for pure-tone bone-conduction audiometry without masking using a manually operated instrument – technical note. Br J Audiol, 1985; 19(4): 281-2.
Oldak M, Ozieblo D, Pollak A, Stepniak I, Lazniewski M, Lechowicz U, et al. Novel neuro-audiological findings and further evidence for TWNK involvement in Perrault syndrome. J Transl Med, 2017; 15(1): 25.
Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, et al. Integrative genomics viewer. Nat Biotechnol, 2011; 29(1): 24-6.
Genomes Project C, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, et al. An integrated map of genetic variation from 1,092 human genomes. Nature, 2012; 491(7422): 56-65.
Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc, 2009; 4(7): 1073-81.
Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet, 2013; Chapter 7: Unit 7 20.
Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods, 2014; 11(4): 361-2.
Gallant E, Francey L, Fetting H, Kaur M, Hakonarson H, Clark D, et al. Novel COCH mutation in a family with autosomal dominant late onset sensorineural hearing impairment and tinnitus. Am J Otolaryngol, 2013; 34(3): 230-5.
Skarzynski H, Lorens A, Piotrowska A. A new method of partial deafness treatment. Med Sci Mon, 2003; 9(4): CS20-4.
Skarzynski H, Lorens A, Piotrowska A, Anderson I. Partial deafness cochlear implantation in children. Int J Ped Otorhinolaryngol, 2007; 71(9): 1407-13.
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