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Deafness pp 17–39Cite as

Molecular Etiology of Deafness and Cochlear Consequences

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Part of the book series: Springer Handbook of Auditory Research ((SHAR,volume 47))

Abstract

Hereditary hearing loss is extremely heterogeneous, represented by mutations in hundreds of genes. These include nuclear and mitochondrial genes, as well as microRNAs. The complexity of the auditory system is thus represented by a multitude of proteins encoded by these genes and regulatory pathways involved in many different functional pathways. A variety of techniques have been used over the years to identify the genes involved in hearing loss, which have evolved significantly with the sequencing of the human genome. Both the costs and the speed with which mutations can be found have changed, transforming the field. Further, the contribution of mouse models for the study of the human deafness genes has been unparalleled. The consequences of the genetic mutations have been elucidated in these mouse models, possible because of the similarity between the human and mouse inner ear structure and genes. More genes have yet to be discovered, which will help complete the knowledge of genotype–phenotype correlations between genetic mutation and type and characteristic of hearing loss. Finally, the genetic basis of deafness will help the discovery of the array of pathways involved in normal and impaired auditory and vestibular function.

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References

  • Bartlett, J. M., & Stirling, D. (2003). A short history of the polymerase chain reaction. Methods in Molecular Biology, 226, 3–6.

    PubMed  CAS  Google Scholar 

  • Beltramello, M., Piazza, V., Bukauskas, F. F., Pozzan, T., & Mammano, F. (2005). Impaired permeability to Ins(1,4,5)P3 in a mutant connexin underlies recessive hereditary deafness. Nature Cell Biology, 7(1), 63–69.

    Article  PubMed  CAS  Google Scholar 

  • Borck, G., Ur Rehman, A., Lee, K., Pogoda, H. M., Kakar, N., von Ameln, S., Grillet, N., Hildebrand, M. S., Ahmed, Z. M., Nurnberg, G., Ansar, M., Basit, S., Javed, Q., Morell, R. J., Nasreen, N., Shearer, A. E., Ahmad, A., Kahrizi, K., Shaikh, R. S., Ali, R. A., Khan, S. N., Goebel, I., Meyer, N. C., Kimberling, W. J., Webster, J. A., Stephan, D. A., Schiller, M. R., Bahlo, M., Najmabadi, H., Gillespie, P. G., Nurnberg, P., Wollnik, B., Riazuddin, S., Smith, R. J., Ahmad, W., Muller, U., Hammerschmidt, M., Friedman, T. B., Leal, S. M., Ahmad, J., & Kubisch, C. (2011). Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42. American Journal of Human Genetics, 88(2), 127–137.

    Article  PubMed  CAS  Google Scholar 

  • Brown, S. D., Wurst, W., Kuhn, R., & Hancock, J. M. (2009). The functional annotation of mammalian genomes: The challenge of phenotyping. Annual Review of Genetics, 43, 305–333.

    Article  PubMed  CAS  Google Scholar 

  • Brownstein, Z., Friedman, L. M., Shahin, H., Oron-Karni, V., Kol, N., Rayyan, A. A., Parzefall, T., Lev, D., Shalev, S., Frydman, M., Davidov, B., Shohat, M., Rahile, M., Lieberman, S., Levy-Lahad, E., Lee, M. K., Shomron, N., King, M. C., Walsh, T., Kanaan, M., & Avraham, K. B. (2011). Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in Middle Eastern families. Genome Biology, 12(9), R89.

    Article  PubMed  CAS  Google Scholar 

  • Capecchi, M. R. (2005). Gene targeting in mice: Functional analysis of the mammalian genome for the twenty-first century. Nature Reviews Genetics, 6(6), 507–512.

    Article  PubMed  CAS  Google Scholar 

  • Chan, D. K., Schrijver, I., & Chang, K. W. (2010). Connexin-26–associated deafness: Phenotypic variability and progression of hearing loss. Genetics in Medicine, 12(3), 174–181.

    Article  PubMed  CAS  Google Scholar 

  • Christianson, A., & Modell, B. (2004). Medical genetics in developing countries. Annual Review of Genomics and Human Genetics, 5, 219–265.

    Article  PubMed  CAS  Google Scholar 

  • Coghill, E. L., Hugill, A., Parkinson, N., Davison, C., Glenister, P., Clements, S., Hunter, J., Cox, R. D., & Brown, S. D. (2002). A gene-driven approach to the identification of ENU mutants in the mouse. Nature Genetics, 30(3), 255–256.

    Article  PubMed  Google Scholar 

  • Cohen-Salmon, M., Ott, T., Michel, V., Hardelin, J. P., Perfettini, I., Eybalin, M., Wu, T., Marcus, D. C., Wangemann, P., Willecke, K., & Petit, C. (2002). Targeted ablation of connexin26 in the inner ear epithelial gap junction network causes hearing impairment and cell death. Current Biology, 12(13), 1106–1111.

    Article  PubMed  CAS  Google Scholar 

  • Common, J. E., Bitner-Glindzicz, M., O’Toole, E. A., Barnes, M. R., Jenkins, L., Forge, A., & Kelsell, D. P. (2005). Specific loss of connexin 26 expression in ductal sweat gland epithelium associated with the deletion mutation del(GJB6–D13S1830). Clinical and Experimental Dermatology, 30(6), 688–693.

    Article  PubMed  CAS  Google Scholar 

  • Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., & Willecke, K. (1996). Molecular cloning and functional expression of mouse connexin-30,a gap junction gene highly expressed in adult brain and skin. The Journal of Biological Chemistry, 271(30), 17903–17910.

    Article  PubMed  CAS  Google Scholar 

  • del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., Siemering, K. R., Weil, D., Wuyts, W., Aguirre, L. A., Martin, Y., Moreno-Pelayo, M. A., Villamar, M., Avraham, K. B., Dahl, H. H., Kanaan, M., Nance, W. E., Petit, C., Smith, R. J., Van Camp, G., Sartorato, E. L., Murgia, A., Moreno, F., & del Castillo, I. (2005). A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. Journal of Medical Genetics, 42(7), 588–594.

    Article  PubMed  Google Scholar 

  • Del Castillo, I., Moreno-Pelayo, M. A., Del Castillo, F. J., Brownstein, Z., Marlin, S., Adina, Q., Cockburn, D. J., Pandya, A., Siemering, K. R., Chamberlin, G. P., Ballana, E., Wuyts, W., Maciel-Guerra, A. T., Alvarez, A., Villamar, M., Shohat, M., Abeliovich, D., Dahl, H. H., Estivill, X., Gasparini, P., Hutchin, T., Nance, W. E., Sartorato, E. L., Smith, R. J., Van Camp, G., Avraham, K. B., Petit, C., & Moreno, F. (2003). Prevalence and evolutionary origins of the del(GJB6–D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: A multicenter study. American Journal of Human Genetics, 73(6), 1452–1458.

    Article  PubMed  Google Scholar 

  • Denoyelle, F., Marlin, S., Weil, D., Moatti, L., Chauvin, P., Garabedian, E. N., & Petit, C. (1999). Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: Implications for genetic counselling. The Lancet, 353(9161), 1298–1303.

    Article  CAS  Google Scholar 

  • Dossena, S., Rodighiero, S., Vezzoli, V., Nofziger, C., Salvioni, E., Boccazzi, M., Grabmayer, E., Botta, G., Meyer, G., Fugazzola, L., Beck-Peccoz, P., & Paulmichl, M. (2009). Functional characterization of wild-type and mutated pendrin (SLC26A4), the anion transporter involved in Pendred syndrome. Journal of Molecular Endocrinology, 43(3), 93–103.

    Article  PubMed  CAS  Google Scholar 

  • Dossena, S., Nofziger, C., Tamma, G., Bernardinelli, E., Vanoni, S., Nowak, C., Grabmayer, E., Kossler, S., Stephan, S., Patsch, W., & Paulmichl, M. (2011). Molecular and functional characterization of human pendrin and its allelic variants. Cellular Physiology and Biochemistry, 28(3), 451–466.

    Article  PubMed  CAS  Google Scholar 

  • Dror, A. A., & Avraham, K. B. (2009a). Hearing loss: Mechanisms revealed by genetics and cell biology. Annual Review of Genetics, 43, 411–437.

    Article  PubMed  CAS  Google Scholar 

  • Dror, A. A., & Avraham, K. B. (2009b). Hearing loss: Mechanisms revealed by genetics and cell biology. Annual Review of Genetics, 43, 411–437.

    Article  PubMed  CAS  Google Scholar 

  • El-Amraoui, A., & Petit, C. (2010). Cadherins as targets for genetic diseases. Cold Spring Harbor Perspectives in Biology, 2(1), a003095.

    Article  PubMed  Google Scholar 

  • Forge, A., Becker, D., Casalotti, S., Edwards, J., Marziano, N., & Nevill, G. (2003). Gap junctions in the inner ear: Comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals. The Journal of Comparative Neurology, 467(2), 207–231.

    Article  PubMed  Google Scholar 

  • Friedman, L. M., Dror, A. A., & Avraham, K. B. (2007). Mouse models to study inner ear development and hereditary hearing loss. International Journal of Developmental Biology, 51(6–7), 609–631.

    Article  PubMed  CAS  Google Scholar 

  • Gabriel, H. D., Jung, D., Butzler, C., Temme, A., Traub, O., Winterhager, E., & Willecke, K. (1998). Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice. Journal of Cell Biology, 140(6), 1453–1461.

    Article  PubMed  CAS  Google Scholar 

  • Gibson, W. P., & Graham, J. M. (2008). Editorial: ‘Auditory neuropathy’ and cochlear implantation—myths and facts. Cochlear Implants International, 9(1), 1–7.

    Article  PubMed  Google Scholar 

  • Gilissen, C., Hoischen, A., Brunner, H. G., & Veltman, J. A. (2012). Disease gene identification strategies for exome sequencing. European Journal of Human Genetics, 20(5), 490–497.

    Article  PubMed  CAS  Google Scholar 

  • Glenn, T. C. (2011). Field guide to next-generation DNA sequencers. Molecular Ecology Resources, 11(5), 759–769.

    Article  PubMed  CAS  Google Scholar 

  • Grifa, A., Wagner, C. A., D’Ambrosio, L., Melchionda, S., Bernardi, F., Lopez-Bigas, N., Rabionet, R., Arbones, M., Monica, M. D., Estivill, X., Zelante, L., Lang, F., & Gasparini, P. (1999). Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nature Genetics, 23(1), 16–18.

    Article  PubMed  CAS  Google Scholar 

  • Grillet, N., Schwander, M., Hildebrand, M. S., Sczaniecka, A., Kolatkar, A., Velasco, J., Webster, J. A., Kahrizi, K., Najmabadi, H., Kimberling, W. J., Stephan, D., Bahlo, M., Wiltshire, T., Tarantino, L. M., Kuhn, P., Smith, R. J., & Muller, U. (2009). Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans. American Journal of Human Genetics, 85(3), 328–337.

    Article  PubMed  CAS  Google Scholar 

  • Hilgert, N., Smith, R. J., & Van Camp, G. (2009). Forty-six genes causing nonsyndromic hearing impairment: Which ones should be analyzed in DNA diagnostics? Mutation Research, 681(2–3), 189–196.

    Article  PubMed  CAS  Google Scholar 

  • Kelsell, D. P., Dunlop, J., Stevens, H. P., Lench, N. J., Liang, J. N., Parry, G., Mueller, R. F., & Leigh, I. M. (1997). Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature, 387(6628), 80–83.

    Article  PubMed  CAS  Google Scholar 

  • Kudo, T., Kure, S., Ikeda, K., Xia, A. P., Katori, Y., Suzuki, M., Kojima, K., Ichinohe, A., Suzuki, Y., Aoki, Y., Kobayashi, T., & Matsubara, Y. (2003). Transgenic expression of a dominant-negative connexin26 causes degeneration of the organ of Corti and non-syndromic deafness. Human Molecular Genetics, 12(9), 995–1004.

    Article  PubMed  CAS  Google Scholar 

  • Lander, E. S., & Botstein, D. (1987). Homozygosity mapping: A way to map human recessive traits with the DNA of inbred children. Science, 236(4808), 1567–1570.

    Article  PubMed  CAS  Google Scholar 

  • Lefevre, G., Michel, V., Weil, D., Lepelletier, L., Bizard, E., Wolfrum, U., Hardelin, J. P., & Petit, C. (2008). A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development, 135(8), 1427–1437.

    Article  PubMed  CAS  Google Scholar 

  • Legan, P. K., Lukashkina, V. A., Goodyear, R. J., Kossi, M., Russell, I. J., & Richardson, G. P. (2000). A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback. Neuron, 28(1), 273–285.

    Article  PubMed  CAS  Google Scholar 

  • Legan, P. K., Lukashkina, V. A., Goodyear, R. J., Lukashkin, A. N., Verhoeven, K., Van Camp, G., Russell, I. J., & Richardson, G. P. (2005). A deafness mutation isolates a second role for the tectorial membrane in hearing. Nature Neuroscience, 8(8), 1035–1042.

    Article  PubMed  CAS  Google Scholar 

  • Leibovici, M., Safieddine, S., & Petit, C. (2008). Mouse models for human hereditary deafness. Current Topics in Developmental Biology, 84, 385–429.

    Article  PubMed  CAS  Google Scholar 

  • Leon, P. E., Raventos, H., Lynch, E., Morrow, J., & King, M. C. (1992). The gene for an inherited form of deafness maps to chromosome 5q31. Proceedings of the National Academy of Sciences of the USA, 89(11), 5181–5184.

    Article  PubMed  CAS  Google Scholar 

  • Mahboubi, H., Dwabe, S., Fradkin, M., Kimonis, V., & Djalilian, H. R. (2012). Genetics of hearing loss: Where are we standing now? European Archives of Oto-Rhino-Laryngology, 269(7), 1733–1745.

    PubMed  Google Scholar 

  • Mahdieh, N., Raeisi, M., Shirkavand, A., Bagherian, H., Akbari, M. T., & Zeinali, S. (2010). Investigation of GJB6 large deletions in Iranian patients using quantitative real-time PCR. Clinical Laboratory, 56(9–10), 467–471.

    PubMed  Google Scholar 

  • Masmoudi, S., Charfedine, I., Hmani, M., Grati, M., Ghorbel, A. M., Elgaied-Boulila, A., Drira, M., Hardelin, J. P., & Ayadi, H. (2000). Pendred syndrome: Phenotypic variability in two families carrying the same PDS missense mutation. American Journal of Medical Genetics, 90(1), 38–44.

    Article  PubMed  CAS  Google Scholar 

  • McHugh, R. K., & Friedman, R. A. (2006). Genetics of hearing loss: Allelism and modifier genes produce a phenotypic continuum. The Anatomical Record, 288(4), 370–381.

    PubMed  Google Scholar 

  • Metzker, M. L. (2010). Sequencing technologies—the next generation. Nature Reviews Genetics, 11(1), 31–46.

    Article  PubMed  CAS  Google Scholar 

  • Nadol, J. B., Jr., & Merchant, S. N. (2001). Histopathology and molecular genetics of hearing loss in the human. International Journal of Pediatric Otorhinolaryngology, 61(1), 1–15.

    Article  PubMed  Google Scholar 

  • Pangrsic, T., Lasarow, L., Reuter, K., Takago, H., Schwander, M., Riedel, D., Frank, T., Tarantino, L. M., Bailey, J. S., Strenzke, N., Brose, N., Muller, U., Reisinger, E., & Moser, T. (2010). Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells. Nature Neuroscience, 13(7), 869–876.

    Article  PubMed  CAS  Google Scholar 

  • Paz, A., Brownstein, Z., Ber, Y., Bialik, S., David, E., Sagir, D., Ulitsky, I., Elkon, R., Kimchi, A., Avraham, K. B., Shiloh, Y., & Shamir, R. (2011). SPIKE: A database of highly curated human signaling pathways. Nucleic Acids Research, 39(Database issue), D793–799.

    Google Scholar 

  • Pera, A., Dossena, S., Rodighiero, S., Gandia, M., Botta, G., Meyer, G., Moreno, F., Nofziger, C., Hernandez-Chico, C., & Paulmichl, M. (2008). Functional assessment of allelic variants in the SLC26A4 gene involved in Pendred syndrome and nonsyndromic EVA. Proceedings of the National Academy of Sciences of the USA, 105(47), 18608–18613.

    Article  PubMed  CAS  Google Scholar 

  • Petit, C. (2001). Usher syndrome: From genetics to pathogenesis. Annual Review of Genomics and Human Genetics, 2, 271–297.

    Article  PubMed  CAS  Google Scholar 

  • Petit, C. (2006). From deafness genes to hearing mechanisms: Harmony and counterpoint. Trends in Molecular Medicine, 12(2), 57–64.

    Article  PubMed  CAS  Google Scholar 

  • Polasek, O., Hayward, C., Bellenguez, C., Vitart, V., Kolcic, I., McQuillan, R., Saftic, V., Gyllensten, U., Wilson, J. F., Rudan, I., Wright, A. F., Campbell, H., & Leutenegger, A. L. (2010). Comparative assessment of methods for estimating individual genome-wide homozygosity-by-descent from human genomic data. BMC Genomics, 11, 139.

    Article  PubMed  Google Scholar 

  • Raphael, Y., & Altschuler, R. A. (2003a). Structure and innervation of the cochlea. Brain Research Bulletin, 60(5–6), 397–422.

    Article  PubMed  Google Scholar 

  • Raphael, Y., & Altschuler, R. A. (2003b). Structure and innervation of the cochlea. Brain Research Bulletin, 60(5–6), 397–422.

    Article  PubMed  Google Scholar 

  • Rehman, A. U., Morell, R. J., Belyantseva, I. A., Khan, S. Y., Boger, E. T., Shahzad, M., Ahmed, Z. M., Riazuddin, S., Khan, S. N., & Friedman, T. B. (2010). Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79. American Journal of Human Genetics, 86(3), 378–388.

    Article  PubMed  CAS  Google Scholar 

  • Richard, G., White, T. W., Smith, L. E., Bailey, R. A., Compton, J. G., Paul, D. L., & Bale, S. J. (1998). Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma. Human Genetics, 103(4), 393–399.

    Article  PubMed  CAS  Google Scholar 

  • Richardson, G. P., de Monvel, J. B., & Petit, C. (2011). How the genetics of deafness illuminates auditory physiology. Annual Review of Physiology, 73, 311–334.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Ballesteros, M., Reynoso, R., Olarte, M., Villamar, M., Morera, C., Santarelli, R., Arslan, E., Meda, C., Curet, C., Volter, C., Sainz-Quevedo, M., Castorina, P., Ambrosetti, U., Berrettini, S., Frei, K., Tedin, S., Smith, J., Cruz Tapia, M., Cavalle, L., Gelvez, N., Primignani, P., Gomez-Rosas, E., Martin, M., Moreno-Pelayo, M. A., Tamayo, M., Moreno-Barral, J., Moreno, F., & del Castillo, I. (2008). A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Human Mutation, 29(6), 823–831.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Paris, J., Pique, L., Colen, T., Roberson, J., Gardner, P., & Schrijver, I. (2010). Genotyping with a 198 mutation arrayed primer extension array for hereditary hearing loss: Assessment of its diagnostic value for medical practice. PLoS One, 5(7), e11804.

    Article  PubMed  Google Scholar 

  • Rouillon, I., Marcolla, A., Roux, I., Marlin, S., Feldmann, D., Couderc, R., Jonard, L., Petit, C., Denoyelle, F., Garabedian, E. N., & Loundon, N. (2006). Results of cochlear implantation in two children with mutations in the OTOF gene. International Journal of Pediatric Otorhinolaryngology, 70(4), 689–696.

    Article  PubMed  CAS  Google Scholar 

  • Roux, I., Safieddine, S., Nouvian, R., Grati, M., Simmler, M. C., Bahloul, A., Perfettini, I., Le Gall, M., Rostaing, P., Hamard, G., Triller, A., Avan, P., Moser, T., & Petit, C. (2006). Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell, 127(2), 277–289.

    Article  PubMed  CAS  Google Scholar 

  • Sachidanandam, R., Weissman, D., Schmidt, S. C., Kakol, J. M., Stein, L. D., Marth, G., Sherry, S., Mullikin, J. C., Mortimore, B. J., Willey, D. L., Hunt, S. E., Cole, C. G., Coggill, P. C., Rice, C. M., Ning, Z., Rogers, J., Bentley, D. R., Kwok, P. Y., Mardis, E. R., Yeh, R. T., Schultz, B., Cook, L., Davenport, R., Dante, M., Fulton, L., Hillier, L., Waterston, R. H., McPherson, J. D., Gilman, B., Schaffner, S., Van Etten, W. J., Reich, D., Higgins, J., Daly, M. J., Blumenstiel, B., Baldwin, J., Stange-Thomann, N., Zody, M. C., Linton, L., Lander, E. S., & Altshuler, D. (2001). A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature, 409(6822), 928–933.

    Article  PubMed  CAS  Google Scholar 

  • Saihan, Z., Webster, A. R., Luxon, L., & Bitner-Glindzicz, M. (2009). Update on Usher syndrome. Current Opinion in Neurology, 22(1), 19–27.

    Article  PubMed  Google Scholar 

  • Sanger, F., Nicklen, S., & Coulson, A. R. (1977). DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences of the USA, 74(12), 5463–5467.

    Article  PubMed  CAS  Google Scholar 

  • Santarelli, R. (2010). Information from cochlear potentials and genetic mutations helps localize the lesion site in auditory neuropathy. Genome Medicine, 2(12), 91.

    Article  PubMed  CAS  Google Scholar 

  • Shahin, H., Walsh, T., Rayyan, A. A., Lee, M. K., Higgins, J., Dickel, D., Lewis, K., Thompson, J., Baker, C., Nord, A. S., Stray, S., Gurwitz, D., Avraham, K. B., King, M. C., & Kanaan, M. (2010). Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families. European Journal of Human Genetics, 18(4), 407–413.

    Article  PubMed  CAS  Google Scholar 

  • Shearer, A. E., DeLuca, A. P., Hildebrand, M. S., Taylor, K. R., Gurrola, J., 2nd, Scherer, S., Scheetz, T. E., & Smith, R. J. (2010). Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proceedings of the National Academy of Sciences of the USA, 107(49), 21104–21109.

    Article  PubMed  CAS  Google Scholar 

  • Shearer, A. E., Hildebrand, M. S., Sloan, C. M., & Smith, R. J. (2011). Deafness in the genomics era. Hearing Research, 282(1–2), 1–9.

    Article  PubMed  Google Scholar 

  • Shinawi, M., & Cheung, S. W. (2008). The array CGH and its clinical applications. Drug Discovery Today, 13(17–18), 760–770.

    Article  PubMed  CAS  Google Scholar 

  • Starr, A., Sininger, Y. S., & Pratt, H. (2000). The varieties of auditory neuropathy. Journal of Basic and Clinical Physiology and Pharmacology, 11(3), 215–230.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki, H., Oshima, A., Tsukamoto, K., Abe, S., Kumakawa, K., Nagai, K., Satoh, H., Kanda, Y., Iwasaki, S., & Usami, S. (2007). Clinical characteristics and genotype-phenotype correlation of hearing loss patients with SLC26A4 mutations. Acta Oto-Laryngologica, 127(12), 1292–1297.

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto, K., Suzuki, H., Harada, D., Namba, A., Abe, S., & Usami, S. (2003). Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: A unique spectrum of mutations in Japanese. European Journal of Human Genetics, 11(12), 916–922.

    Article  PubMed  CAS  Google Scholar 

  • Verhoeven, K., Van Laer, L., Kirschhofer, K., Legan, P. K., Hughes, D. C., Schatteman, I., Verstreken, M., Van Hauwe, P., Coucke, P., Chen, A., Smith, R. J., Somers, T., Offeciers, F. E., Van de Heyning, P., Richardson, G. P., Wachtler, F., Kimberling, W. J., Willems, P. J., Govaerts, P. J., & Van Camp, G. (1998). Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nature Genetics, 19(1), 60–62.

    Article  PubMed  CAS  Google Scholar 

  • Vignal, A., Milan, D., SanCristobal, M., & Eggen, A. (2002). A review on SNP and other types of molecular markers and their use in animal genetics. Genetics Selection Evolution, 34(3), 275–305.

    Article  CAS  Google Scholar 

  • Vrijens, K., Van Laer, L., & Van Camp, G. (2008). Human hereditary hearing impairment: Mouse models can help to solve the puzzle. Human Genetics, 124(4), 325–348.

    Article  PubMed  Google Scholar 

  • Walsh, T., Pierce, S. B., Lenz, D. R., Brownstein, Z., Dagan-Rosenfeld, O., Shahin, H., Roeb, W., McCarthy, S., Nord, A. S., Gordon, C. R., Ben-Neriah, Z., Sebat, J., Kanaan, M., Lee, M. K., Frydman, M., King, M. C., & Avraham, K. B. (2010a). Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51. American Journal of Human Genetics, 87(1), 101–109.

    Article  PubMed  CAS  Google Scholar 

  • Walsh, T., Shahin, H., Elkan-Miller, T., Lee, M. K., Thornton, A. M., Roeb, W., Abu Rayyan, A., Loulus, S., Avraham, K. B., King, M. C., & Kanaan, M. (2010b). Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. American Journal of Human Genetics, 87(1), 90–94.

    Article  PubMed  CAS  Google Scholar 

  • Wang, J., Fan, Y. Y., Wang, S. J., Liang, P. F., Wang, J. L. & Qiu, J. H. (2011). Variants of OTOF and PJVK genes in Chinese patients with auditory neuropathy spectrum disorder. PLoS One, 6(9), e24000.

    Article  PubMed  CAS  Google Scholar 

  • Wangemann, P., Itza, E. M., Albrecht, B., Wu, T., Jabba, S. V., Maganti, R. J., Lee, J. H., Everett, L. A., Wall, S. M., Royaux, I. E., Green, E. D. & Marcus, D. C. (2004). Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model. BMC Medicine, 2, 30.

    Article  PubMed  Google Scholar 

  • Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., An, P., Antonarakis, S. E., Attwood, J., Baertsch, R., Bailey, J., Barlow, K., Beck, S., Berry, E., Birren, B., Bloom, T., Bork, P., Botcherby, M., Bray, N., Brent, M. R., Brown, D. G., Brown, S. D., Bult, C., Burton, J., Butler, J., Campbell, R. D., Carninci, P., Cawley, S., Chiaromonte, F., Chinwalla, A. T., Church, D. M., Clamp, M., Clee, C., Collins, F. S., Cook, L. L., Copley, R. R., Coulson, A., Couronne, O., Cuff, J., Curwen, V., Cutts, T., Daly, M., David, R., Davies, J., Delehaunty, K. D., Deri, J., Dermitzakis, E. T., Dewey, C., Dickens, N. J., Diekhans, M., Dodge, S., Dubchak, I., Dunn, D. M., Eddy, S. R., Elnitski, L., Emes, R. D., Eswara, P., Eyras, E., Felsenfeld, A., Fewell, G. A., Flicek, P., Foley, K., Frankel, W. N., Fulton, L. A., Fulton, R. S., Furey, T. S., Gage, D., Gibbs, R. A., Glusman, G., Gnerre, S., Goldman, N., Goodstadt, L., Grafham, D., Graves, T. A., Green, E. D., Gregory, S., Guigo, R., Guyer, M., Hardison, R. C., Haussler, D., Hayashizaki, Y., Hillier, L. W., Hinrichs, A., Hlavina, W., Holzer, T., Hsu, F., Hua, A., Hubbard, T., Hunt, A., Jackson, I., Jaffe, D. B., Johnson, L. S., Jones, M., Jones, T. A., Joy, A., Kamal, M., Karlsson, E. K., Karolchik, D., Kasprzyk, A., Kawai, J., Keibler, E., Kells, C., Kent, W. J., Kirby, A., Kolbe, D. L., Korf, I., Kucherlapati, R. S., Kulbokas, E. J., Kulp, D., Landers, T., Leger, J. P., Leonard, S., Letunic, I., Levine, R., Li, J., Li, M., Lloyd, C., Lucas, S., Ma, B., Maglott, D. R., Mardis, E. R., Matthews, L., Mauceli, E., Mayer, J. H., McCarthy, M., McCombie, W. R., McLaren, S., McLay, K., McPherson, J. D., Meldrim, J., Meredith, B., Mesirov, J. P., Miller, W., Miner, T. L., Mongin, E., Montgomery, K. T., Morgan, M., Mott, R., Mullikin, J. C., Muzny, D. M., Nash, W. E., Nelson, J. O., Nhan, M. N., Nicol, R., Ning, Z., Nusbaum, C., O’Connor, M. J., Okazaki, Y., Oliver, K., Overton-Larty, E., Pachter, L., Parra, G., Pepin, K. H., Peterson, J., Pevzner, P., Plumb, R., Pohl, C. S., Poliakov, A., Ponce, T. C., Ponting, C. P., Potter, S., Quail, M., Reymond, A., Roe, B. A., Roskin, K. M., Rubin, E. M., Rust, A. G., Santos, R., Sapojnikov, V., Schultz, B., Schultz, J., Schwartz, M. S., Schwartz, S., Scott, C., Seaman, S., Searle, S., Sharpe, T., Sheridan, A., Shownkeen, R., Sims, S., Singer, J. B., Slater, G., Smit, A., Smith, D. R., Spencer, B., Stabenau, A., Stange-Thomann, N., Sugnet, C., Suyama, M., Tesler, G., Thompson, J., Torrents, D., Trevaskis, E., Tromp, J., Ucla, C., Ureta-Vidal, A., Vinson, J. P., Von Niederhausern, A. C., Wade, C. M., Wall, M., Weber, R. J., Weiss, R. B., Wendl, M. C., West, A. P.,Wetterstrand, K., Wheeler, R., Whelan, S., Wierzbowski, J., Willey, D., Williams, S., Wilson, R. K., Winter, E., Worley, K. C., Wyman, D., Yang, S., Yang, S. P., Zdobnov, E. M., Zody, M. C., & Lander, E. S. (2002). Initial sequencing and comparative analysis of the mouse genome. Nature, 420(6915), 520–562.

    Google Scholar 

  • Weber, J. L., & May, P. E. (1989). Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. American Journal of Human Genetics, 44(3), 388–396.

    PubMed  CAS  Google Scholar 

  • Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., & Smith, R. J. (2007). Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4). American Journal of Human Genetics, 80(6), 1055–1063.

    Article  PubMed  CAS  Google Scholar 

  • Yang, T., Gurrola, J. G., 2nd, Wu, H., Chiu, S. M., Wangemann, P., Snyder, P. M., & Smith, R. J. (2009). Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome. American Journal of Human Genetics, 84(5), 651–657.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Research in the Avraham laboratory is funded by the Israel Science Foundation Grant 1320/11, National Institutes of Health (NIDCD) R01DC011835, and I-CORE Gene Regulation in Complex Human Disease, Center No. 41/11. We thank Amiel Dror and Michel Leibovici for figures.

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Authors and Affiliations

  1. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Zippora Brownstein, Shaked Shivatzki & Karen B. Avraham

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  1. Zippora Brownstein
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  2. Shaked Shivatzki
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  3. Karen B. Avraham
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Correspondence to Karen B. Avraham .

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  1. Hannover Medical School, Institute of Audioneurotechnology, Hannover, Germany

    Andrej Kral

  2. Department of Biology, University of Maryland, College Park, Maryland, USA

    Arthur N. Popper

  3. Marine Biological Laboratory, Woods Hole, Massachusetts, USA

    Richard R. Fay

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Brownstein, Z., Shivatzki, S., Avraham, K.B. (2013). Molecular Etiology of Deafness and Cochlear Consequences. In: Kral, A., Popper, A., Fay, R. (eds) Deafness. Springer Handbook of Auditory Research, vol 47. Springer, New York, NY. https://doi.org/10.1007/2506_2013_2

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