A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

Asli Sirmaci, Seyra Erbek, Justin Price, Mingqian Huang, Duygu Duman, F. Başak Cengiz, Güney Bademci, Suna Tokgöz-Yilmaz, Burcu Hişmi, Hilal Özdaǧ, Banu Öztürk, Sevsen Kulaksizoǧlu, Erkan Yildirim, Haris Kokotas, Maria Grigoriadou, Michael B. Petersen, Hashem Shahin, Moien Kanaan, Mary Claire King, Zheng Yi ChenSusan H Blanton, Xue Z Liu, Stephan L Zuchner, Nejat Akar, Mustafa Tekin

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

More 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 (DFNB91) 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 DFNB91 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.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalAmerican Journal of Human Genetics
Volume86
Issue number5
DOIs
StatePublished - May 14 2010

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Hearing Loss
Deafness
Inner Ear
Inner Auditory Hair Cells
Mutation
Sensorineural Hearing Loss
Nonsense Codon
Homozygote
Protease Inhibitors
Genes
Leukocytes
Cell Death
Messenger RNA
Nonsyndromic sensorineural hearing loss
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss. / Sirmaci, Asli; Erbek, Seyra; Price, Justin; Huang, Mingqian; Duman, Duygu; Cengiz, F. Başak; Bademci, Güney; Tokgöz-Yilmaz, Suna; Hişmi, Burcu; Özdaǧ, Hilal; Öztürk, Banu; Kulaksizoǧlu, Sevsen; Yildirim, Erkan; Kokotas, Haris; Grigoriadou, Maria; Petersen, Michael B.; Shahin, Hashem; Kanaan, Moien; King, Mary Claire; Chen, Zheng Yi; Blanton, Susan H; Liu, Xue Z; Zuchner, Stephan L; Akar, Nejat; Tekin, Mustafa.

In: American Journal of Human Genetics, Vol. 86, No. 5, 14.05.2010, p. 797-804.

Research output: Contribution to journalArticle

Sirmaci, A, Erbek, S, Price, J, Huang, M, Duman, D, Cengiz, FB, Bademci, G, Tokgöz-Yilmaz, S, Hişmi, B, Özdaǧ, H, Öztürk, B, Kulaksizoǧlu, S, Yildirim, E, Kokotas, H, Grigoriadou, M, Petersen, MB, Shahin, H, Kanaan, M, King, MC, Chen, ZY, Blanton, SH, Liu, XZ, Zuchner, SL, Akar, N & Tekin, M 2010, 'A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss', American Journal of Human Genetics, vol. 86, no. 5, pp. 797-804. https://doi.org/10.1016/j.ajhg.2010.04.004
Sirmaci, Asli ; Erbek, Seyra ; Price, Justin ; Huang, Mingqian ; Duman, Duygu ; Cengiz, F. Başak ; Bademci, Güney ; Tokgöz-Yilmaz, Suna ; Hişmi, Burcu ; Özdaǧ, Hilal ; Öztürk, Banu ; Kulaksizoǧlu, Sevsen ; Yildirim, Erkan ; Kokotas, Haris ; Grigoriadou, Maria ; Petersen, Michael B. ; Shahin, Hashem ; Kanaan, Moien ; King, Mary Claire ; Chen, Zheng Yi ; Blanton, Susan H ; Liu, Xue Z ; Zuchner, Stephan L ; Akar, Nejat ; Tekin, Mustafa. / A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss. In: American Journal of Human Genetics. 2010 ; Vol. 86, No. 5. pp. 797-804.
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AU - Erbek, Seyra

AU - Price, Justin

AU - Huang, Mingqian

AU - Duman, Duygu

AU - Cengiz, F. Başak

AU - Bademci, Güney

AU - Tokgöz-Yilmaz, Suna

AU - Hişmi, Burcu

AU - Özdaǧ, Hilal

AU - Öztürk, Banu

AU - Kulaksizoǧlu, Sevsen

AU - Yildirim, Erkan

AU - Kokotas, Haris

AU - Grigoriadou, Maria

AU - Petersen, Michael B.

AU - Shahin, Hashem

AU - Kanaan, Moien

AU - King, Mary Claire

AU - Chen, Zheng Yi

AU - Blanton, Susan H

AU - Liu, Xue Z

AU - Zuchner, Stephan L

AU - Akar, Nejat

AU - Tekin, Mustafa

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