A Truncating Mutation in Serpinb6 is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

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dc.contributor.authorSırmacı, Aslı
dc.contributor.authorErbek, Seyra
dc.contributor.authorPrice, Justin
dc.contributor.authorHuang, Mingqian
dc.contributor.authorDuman, Duygu
dc.contributor.authorCengiz, F. Başak
dc.contributor.authorBademci, Güney
dc.contributor.authorYılmaz, Suna Tokgöz
dc.contributor.authorHişmi, Burcu
dc.contributor.authorÖzdağ, Hilal
dc.contributor.authorÖztürk, Banu
dc.contributor.authorKulaksızoğlu, Sevsen
dc.contributor.authorYıldırım, Erkan
dc.contributor.authorKokotaş, Haris
dc.contributor.authorGrigoriadou, Maria
dc.contributor.authorPetersen, B. Michael
dc.contributor.authorShahin, Hashem
dc.contributor.authorKanaan, Moien
dc.contributor.authorKing, Mary-Claire
dc.contributor.authorChen, Zheng-Yi
dc.contributor.authorBlanton, Susan H.
dc.contributor.authorLiu, Xue Z.
dc.contributor.authorZuchner, Stephan
dc.contributor.authorAkar, Nejat
dc.contributor.authorTekin, Mustafa
dc.date.accessioned2020-03-26T17:46:51Z
dc.date.available2020-03-26T17:46:51Z
dc.date.issued2010
dc.departmentSelçuk Üniversitesien_US
dc.description.abstractMore than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DENB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DENB91 and encodes for an intracellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. We also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells. We propose that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress and that loss of this protection results in cell death and sensorineural hearing loss.en_US
dc.description.sponsorshipThe Scientific AMP; Technological Research Council of Turkey [105S464, 108S045]; University of Miami; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 DC006908]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30728030]; Federick and Ines Yeatts [R01 DC005575]; Oticon Fonden, Denmarken_US
dc.description.sponsorshipWe are thankful to all participating families. We thank Professor Phillip I. Bird from Monash University, Australia, for helpful suggestions and critical reading of the manuscript. This study was partially supported by The Scientific & Technological Research Council of Turkey Grants (105S464 and 108S045), funds from the University of Miami to M.T., NIH R01 DC006908 to Z.-Y.C., National Natural Science Foundation of China to Z.-Y.C. (30728030), the Federick and Ines Yeatts inner ear hair cell regeneration fellowship to M.H., R01 DC005575 to X.Z.L., and a grant from Oticon Fonden, Denmark, to M.B.P.en_US
dc.identifier.citationSırmacı, A., Erbek, S., Price, J., Huang, M., Duman, D., Cengiz, F. B., Bademci, G., Yılmaz, S. T., Hişmi, B., Özdağ, H., Öztürk, B., Kulaksızoğlu, S., Yıldırım, E., Kokotaş, H., Grigoriadou, M., Petersen, B. M., Shahin, H., Kanaan, M., King, M.-C., Chen, Z.-Y., Blanton, S. H., Liu, X. Z., Zuchner, S., Akar, N., Tekin, M., (2010). A Truncating Mutation in Serpinb6 is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss. American Journal of Human Genetics, (86), 797-804. Doi: 10.1016/j.ajhg.2010.04.004
dc.identifier.doi10.1016/j.ajhg.2010.04.004en_US
dc.identifier.endpage804en_US
dc.identifier.issn0002-9297en_US
dc.identifier.issn1537-6605en_US
dc.identifier.pmid20451170en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage797en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.ajhg.2010.04.004
dc.identifier.urihttps://hdl.handle.net/20.500.12395/24563
dc.identifier.volume86en_US
dc.identifier.wosWOS:000278045300016en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorÖztürk, Banu
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.titleA Truncating Mutation in Serpinb6 is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Lossen_US
dc.typeArticleen_US

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