Abstract
TECTA gene encodes α-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype–phenotype correlations are associated with mutations of TECTA in exons according to α-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype–phenotype correlation, as well as the intracellular localization of missense mutations in the α-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype–phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of α-tectorin into the tectorial membrane.
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References
Smith, R. J., Bale, Jr J. F. & White, K. R. Sensorineural hearing loss in children. Lancet 365, 879–890 (2005).
Petersen, M. B. & Willems, P. J. Non-syndromic, autosomal-recessive deafness. Clin. Genet. 69, 371–392 (2006).
Verhoeven, K., Van Laer, L., Kirschhofer, K., Legan, P. K., Hughes, D. C., Schatteman, I. et al. Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nat. Genet. 19, 60–62 (1998).
Moreno-Pelayo, M. A., del Castillo, I., Villamar, M., Romero, L., Hernandez-Calvin, F. J., Herraiz, C. et al. A cysteine substitution in the zona pellucida domain of alpha-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family. J. Med. Genet. 38, E13 (2001).
Iwasaki, S., Harada, D., Usami, S., Nagura, M., Takeshita, T. & Hoshino, T. Association of clinical features with mutation of TECTA in a family with autosomal dominant hearing loss. Arch. Otolaryngol. Head Neck Surg. 128, 913–917 (2002).
Plantinga, R. F., de Brouwer, A. P., Huygen, P. L., Kunst, H. P., Kremer, H. & Cremers, C. W. A novel TECTA mutation in a Dutch DFNA8/12 family confirms genotype-phenotype correlation. J. Assoc. Res. Otolaryngol. 7, 173–181 (2006).
Sagong, B., Park, R., Kim, Y. H., Lee, K. Y., Baek, J. I., Cho, H. J. et al. Two novel missense mutations in the TECTA gene in Korean families with autosomal dominant nonsyndromic hearing loss. Ann. Clin. Lab. Sci. 40, 380–385 (2010).
Hildebrand, M. S., Morin, M., Meyer, N. C., Mayo, F., Modamio-Hoybjor, S., Mencia, A. et al. DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss. Hum. Mutat. 32, 825–834 (2011).
de Heer, A. R., Pauw, R. J., Huygen, P. L., Collin, R. W., Kremer, H. & Cremers, C. W. Flat threshold and mid-frequency hearing impairment in a Dutch DFNA8/12 family with a novel mutation in TECTA. Some evidence for protection of the inner ear. Audiol. Neurootol. 14, 153–162 (2009).
Balciuniene, J., Dahl, N., Jalonen, P., Verhoeven, K., Van Camp, G., Borg, E. et al. Alpha-tectorin involvement in hearing disabilities: one gene--two phenotypes. Hum. Genet. 105, 211–216 (1999).
Legan, P. K., Lukashkina, V. A., Goodyear, R. J., Kossi, M., Russell, I. J. & Richardson, G. P. A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback. Neuron 28, 273–285 (2000).
Plantinga, R. F., Cremers, C. W., Huygen, P. L., Kunst, H. P. & Bosman, A. J. Audiological evaluation of affected members from a Dutch DFNA8/12 (TECTA) family. J. Assoc. Res. Otolaryngol. 8, 1–7 (2007).
Sarkar, G. & Sommer, S. S. The ‘megaprimer’ method of site-directed mutagenesis. Biotechniques 8, 404–407 (1990).
Govaerts, P. J., De Ceulaer, G., Daemers, K., Verhoeven, K., Van Camp, G., Schatteman, I. et al. A new autosomal-dominant locus (DFNA12) is responsible for a nonsyndromic, midfrequency, prelingual and nonprogressive sensorineural hearing loss. Am. J. Otol. 19, 718–723 (1998).
Moreno-Pelayo, M. A., Goodyear, R. J., Mencia, A., Modamio-Hoybjor, S., Legan, P. K., Olavarrieta, L. et al. Characterization of a spontaneous, recessive, missense mutation arising in the Tecta gene. J. Assoc. Res. Otolaryngol. 9, 202–214 (2008).
Pfister, M., Thiele, H., Van Camp, G., Fransen, E., Apaydin, F., Aydin, O. et al. A genotype-phenotype correlation with gender-effect for hearing impairment caused by TECTA mutations. Cell Physiol. Biochem. 14, 369–376 (2004).
Jovine, L., Qi, H., Williams, Z., Litscher, E. & Wassarman, P. M. The ZP domain is a conserved module for polymerization of extracellular proteins. Nat. Cell. Biol. 4, 457–461 (2002).
Qi, H., Williams, Z. & Wassarman, P. M. Secretion and assembly of zona pellucida glycoproteins by growing mouse oocytes microinjected with epitope-tagged cDNAs for mZP2 and mZP3. Mol. Biol. Cell 13, 530–541 (2002).
Jovine, L., Darie, C. C., Litscher, E. S. & Wassarman, P. M. Zona pellucida domain proteins. Ann. Rev. Biochem. 74, 83–114 (2005).
Acknowledgements
We sincerely thank the families for their participation in this study. And we also thank AC Apple-Mathews for help in preparing the manuscript. This work was supported by the Ministry of Health and Welfare, Japan (SU), and a grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (SU).
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Moteki, H., Nishio, Sy., Hashimoto, S. et al. TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion. J Hum Genet 57, 587–592 (2012). https://doi.org/10.1038/jhg.2012.73
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DOI: https://doi.org/10.1038/jhg.2012.73
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