2. Academic Validation
  3. A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss

A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss

  • Am J Hum Genet. 2010 May 14;86(5):797-804. doi: 10.1016/j.ajhg.2010.04.004.
Asli Sirmaci 1,  Seyra Erbek,  Justin Price,  Mingqian Huang,  Duygu Duman,  F Başak Cengiz,  Güney Bademci,  Suna Tokgöz-Yilmaz,  Burcu Hişmi,  Hilal Ozdağ,  Banu Oztürk,  Sevsen Kulaksizoğlu,  Erkan Yildirim,  Haris Kokotas,  Maria Grigoriadou,  Michael B Petersen,  Hashem Shahin,  Moien Kanaan,  Mary-Claire King,  Zheng-Yi Chen,  Susan H Blanton,  Xue Z Liu,  Stephan Zuchner,  Nejat Akar,  Mustafa Tekin
Affiliations

Affiliation

  • 1 Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
PMID: 20451170 DOI: 10.1016/j.ajhg.2010.04.004
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.

Figures