Original Paper

Cochlin-Tomoprotein: A Novel Perilymph-Specific Protein and a Potential Marker for the Diagnosis of Perilymphatic Fistula
Tetsuo Ikezono^a, Susumu Shindo^a, Satomi Sekiguchi^b, Charuk Hanprasertpong^{a, i}, Lishu Li^a, Ruby Pawankar^a, Toshio Morizane^d, Shunkichi Baba^a, Yasuo Koizumi^a, Kuwon Sekine^a, Atsushi Watanabe^c, Atsushi Komatsuzaki^e, Shingo Murakami^f, Toshimitsu Kobayashi^g, Masakazu Miura^h, Toshiaki Yagi<sup>a

a</sup>Department of Otorhinolaryngology, Nippon Medical School,
^bR&D and Business Development Segment, Mitsubishi Chemical Medience Corporation, and
^cDepartment of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo,
^dDepartment of Medicine, Kanagawa Dental College, Kanagawa,
^eNeurootology Clinic, Chiba,
^fDepartment of Otorhinolaryngology, Nagoya City University, Aichi,
^gDepartment of Otolaryngology - Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai,
^hDepartment of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan;
ⁱDepartment of Otorhinolaryngology, Chiangmai University, Chiangmai, Thailand

Address of Corresponding Author

Audiol Neurotol 2009;14:338-344 (DOI: 10.1159/000212113)

  Key Words

• COCH gene
• Cochlin isoform
• Cochlin tomoprotein
• Hearing loss
• Vertigo

  Abstract

Background: Perilymphatic fistula (PLF) is an abnormal connection between the inner and middle ear. A procedure for obtaining definite proof of a PLF remains elusive, and methods of diagnosis remain controversial. To date, there is no clinically relevant biochemical marker for perilymph leakage. Using proteomic analysis of inner ear proteins, we have previously found unique properties of cochlin, encoded by the COCH gene. We detected 3 cochlin isoforms (p63s, p44s and p40s) in the inner ear tissue and a short 16-kDa isoform of cochlin-tomoprotein (CTP) in the perilymph. Since cochlin was found to be highly specific to the inner ear, we speculated that CTP might also be specific to the perilymph. The aim of this study was to determine whether CTP, a novel perilymph-specific protein, could be used as a marker for the diagnosis of PLF. Methods: By Western blotting, we investigated the specificity of CTP expression in a range of body fluids that included perilymph, serum, saliva and cerebrospinal fluid. To elucidate the detection limit of CTP, serially diluted recombinant human (rh)CTP as well as human perilymph was tested. Results: CTP was selectively expressed in all 20 perilymph samples tested, but not in 77 samples of the other body fluids. The detection limit of rhCTP was 0.27 ng or 0.022 µl of perilymph per well on Western blot analysis. Conclusion: The results strongly suggest that CTP can be a specific marker of perilymph leakage. Moreover, CTP has the potential to be a biochemical marker that allows a definitive diagnosis of the etiology of PLF-related hearing loss and vestibular disorders.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Tetsuo Ikezono, MD, PhD
Department of Otorhinolaryngology
Nippon Medical School 1-1-5
Sendagi, Bunkyo-ku, Tokyo 113-8603 (Japan)
Tel. +81 3 3822 2131, ext. 6746, Fax +81 3 5685 0830, E-Mail ctp16kdaplf@nms.ac.jp

  Article Information

Received: December 16, 2008
Accepted after revision: January 16, 2009
Published online: April 15, 2009
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 1, Number of References : 41