Skip Navigation



Human Molecular Genetics Advance Access published online on February 15, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl022
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
15/7/1071    most recent
ddl022v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Robertson, N. G.
Right arrow Articles by Morton, C. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Robertson, N. G.
Right arrow Articles by Morton, C. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved
Received November 25, 2005
Revised February 7, 2006
Accepted February 7, 2006

Article

Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction

Nahid G. Robertson 1, Cor W.R.J. Cremers 2, Patrick L.M. Huygen 2, Tetsuo Ikezono 3, Bryan Krastins 4, Hannie Kremer 2, Sharon F. Kuo 1, M. Charles Liberman 5, Saumil N. Merchant 5, Constance E. Miller 5, Joseph B. Nadol Jr. 5, David A. Sarracino 4, Wim I.M. Verhagen 6, and Cynthia C. Morton 1 *

1 Departments of Pathology, Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
2 Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands
3 Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan
4 Harvard Medical School-Partners Healthcare Center for Genetics and Genomics, Cambridge, Massachusetts, USA
5 Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Eaton-Peabody Laboratory, Harvard Medical School Boston, MA, USA
6 Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

* To whom correspondence should be addressed.
Cynthia C. Morton, E-mail: cmorton{at}partners.org


  Abstract

Seven missense mutations and one in-frame deletion mutation have been reported in the COCH (coagulation factor Chomology) gene, causing the adult-onset, progressive sensorineural hearing loss and vestibular disorder at the DFNA9 locus. Prevalence of COCH mutations worldwide is unknown, as there is no systematic screening effort for late-onset hearing disorders; however, to date, COCH mutations have been found on four continents, and the possibility of COCH playing an important role in presbycusis and disorders of imbalance has been considered. Cochlin (encoded by COCH) has also been shown as a major target antigen for autoimmune sensorineural hearing loss. In this report, we present histopathology, immunohistochemistry, and proteomic analyses of inner ear tissues from post-mortem DFNA9 temporal bone samples of an individual from a large Dutch kindred segregating the P51S mutation and adult human unaffected controls, and wild-type (+/ + ) and Coch null (-/-) knock-out mice. DFNA9 is an inner ear disorder with a unique histopathology showing loss of cellularity and aggregation of abundant homogeneous acellular eosinophilic deposits in the cochlear and vestibular labyrinths, similar to protein aggregation in well-known neurodegenerative disorders. By immunohistochemistry on the DFNA9 temporal bone sections, we have shown cochlin staining of the characteristic cochlear and vestibular deposits, indicating aggregation of cochlin in the same structures in which it is normally expressed. Proteomic analysis identified cochlin as the most abundant protein in mouse and human cochleae. The high-level expression and stability of cochlin in the inner ear, even in the absence and severe atrophy of the fibrocytes that normally express COCH, are shown through these studies and further elucidate the pathobiologic events occurring in DFNA9 leading to hearing loss and vestibular dysfunction.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 IOVSHome page
S. K. Bhattacharya, B. T. Gabelt, J. Ruiz, R. Picciani, and P. L. Kaufman
Cochlin Expression in Anterior Segment Organ Culture Models after TGF{beta}2 Treatment
Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 551 - 559.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
N. G. Robertson, S. M. Jones, T. A. Sivakumaran, A. B.S. Giersch, S. A. Jurado, L. M. Call, C. E. Miller, S. F. Maison, M. C. Liberman, and C. C. Morton
A targeted Coch missense mutation: a knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction
Hum. Mol. Genet., November 1, 2008; 17(21): 3426 - 3434.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.