| First Author | Sirmaci A | Year | 2010 |
| Journal | Am J Hum Genet | Volume | 86 |
| Issue | 5 | Pages | 797-804 |
| PubMed ID | 20451170 | Mgi Jnum | J:164931 |
| Mgi Id | MGI:4835637 | Doi | 10.1016/j.ajhg.2010.04.004 |
| Citation | Sirmaci A, et al. (2010) A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss. Am J Hum Genet 86(5):797-804 |
| abstractText | 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. |
