Medical Genetics in the Clinical Practice of ORL

Editor(s): Alford R.L. (Houston, Tex.) 
Sutton V.R. (Houston, Tex.) 
Table of Contents
Vol. 70, 2011
Section title: Paper
Alford RL, Sutton VR (eds): Medical Genetics in the Clinical Practice of ORL. Adv Otorhinolaryngol. Basel, Karger, 2011, vol 70, pp 56–65

Usher Syndrome: Hearing Loss with Vision Loss

Friedman T.B. · Schultz J.M. · Ahmed Z.M. · Tsilou E.T. · Brewer C.C.
aSection on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Rockville, Md., bDivision of Pediatric Ophthalmology, Cincinnati Children’s Hospital Research Foundation, and Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, cOphthalmic Genetics and Visual Function Branch, National Eye Institute, and dOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Usher syndrome (USH) is a clinically heterogeneous condition characterized by sensorineural hearing loss, progressive retinal degeneration, and vestibular dysfunction. A minimum test battery is described as well as additional clinical evaluations that would provide comprehensive testing of hearing, vestibular function, and visual function in USH patients. USH is also genetically heterogeneous. At least nine genes have been identified with mutations that can cause USH. The proteins encoded by these genes are thought to interact with one another to form a network in the sensory cells of the inner ear and retina.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Brownstein Z Ben-Yosef T Dagan O Frydman M Abeliovich D Sagi M Abraham FA Taitelbaum-Swead R Shohat M Hildesheimer M Friedman TB Avraham KB: The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with non-syndromic hearing loss foreshadows retinitis pigmentosa. Pediatr Res 2004;55:995-1000
  2. Ahmed ZM Riazuddin S Wilcox ER: The molecular genetics of Usher syndrome. Clin Genet 2003;63:431-444
  3. Moller CG Kimberling WJ Davenport SL Priluck I White V Biscone-Halterman K Odkvist LM Brookhouser PE Lund G Grissom TJ: Usher syndrome: an otoneurologic study. Laryngoscope 1989;99:73-79
  4. Saihan Z Webster AR Luxon L Bitner-Glindzicz M: Update on Usher syndrome. Curr Opin Neurol 2009;22:19-27
  5. Adato A Michel V Kikkawa Y Reiners J Alagramam KN Weil D Yonekawa H Wolfrum U El-Amraoui A Petit C: Interactions in the network of Usher syndrome type 1 proteins. Hum Mol Genet 2005;14:347-356
  6. Maerker T van Wijk E Overlack N Kersten FF McGee J Goldmann T Sehn E Roepman R Walsh EJ Kremer H Wolfrum U: A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet 2008;17:71-86
  7. Smith RJ Berlin CI Hejtmancik JF Keats BJ Kimberling WJ Lewis RA Moller CG Pelias MZ Tranebjaerg L: Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet 1994;50:32-38
  8. Young NM Mets MB Hain TC: Early diagnosis of Usher syndrome in infants and children. Am J Otol 1996;17:30-34
  9. Boughman JA Vernon M Shaver KA: Usher syndrome: definition and estimate of prevalence from two high-risk populations. J Chron Dis 1983;36:595-603
  10. Pakarinen L Tuppurainen K Laippala P Mantyjarvi M Puhakka H: The ophthalmological course of Usher syndrome type III. Int Ophthalmol 1995;19:307-311
  11. Drayna D: Founder mutations. Sci Am 2005;293:78-85
  12. Astuto LM Bork JM Weston MD, et al: CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and non-syndromic deafness. Am J Hum Genet 2002;71:262-275
  13. Liu XZ Hope C Walsh J Newton V Ke XM Liang CY Xu LR Zhou JM Trump D Steel KP Bundey S Brown SD: Mutations in the myosin VIIA gene cause a wide phenotypic spectrum, including atypical Usher syndrome. Am J Hum Genet 1998;63:909-912
  14. Bernal S Meda C Solans T Ayuso C Garcia-Sandoval B Valverde D Del Rio E Baiget M: Clinical and genetic studies in Spanish patients with Usher syndrome type II: description of new mutations and evidence for a lack of genotype-phenotype correlation. Clin Genet 2005;68:204-214
  15. Pennings RJ Huygen PL Weston MD van Aarem A Wagenaar M Kimberling WJ Cremers CW: Pure tone hearing thresholds and speech recognition scores in Dutch patients carrying mutations in the USH2A gene. Otol Neurotol 2003;24:58-63
  16. Ness SL Ben-Yosef T Bar-Lev A Madeo AC Brewer CC Avraham KB Kornreich R Desnick RJ Willner JP Friedman TB Griffith AJ: Genetic homogeneity and phenotypic variability among Ashkenazi Jews with Usher syndrome type III. J Med Genet 2003;40:767-772
  17. Sadeghi M Cohn ES Kimberling WJ Tranebjaerg L Moller C: Audiological and vestibular features in affected subjects with USH3: a genotype/phenotype correlation. Int J Audiol 2005;44:307-316
  18. Mets MB Young NM Pass A Lasky JB: Early diagnosis of Usher syndrome in children. Trans Am Ophthalmol Soc 2000;98:237-242
  19. Sharma A Dorman MF Kral A: The influence of a sensitive period on central auditory development in children with unilateral and bilateral cochlear implants. Hear Res 2005;203:134-143
  20. Kumar A Fishman G Torok N: Vestibular and auditory function in Usher’s syndrome. Ann Otol Rhinol Laryngol 1984;93:600-608
  21. Teschner M Neuburger J Gockeln R Lenarz T Lesinski-Schiedat A: ‘Minimized rotational vestibular testing’ as a screening procedure detecting vestibular areflexy in deaf children: screening cochlear implant candidates for Usher syndrome type I. Eur Arch Otorhinolaryngol 2008;265:759-763
  22. Sadeghi AM Eriksson K Kimberling WJ Sjostrom A Moller C: Longterm visual prognosis in Usher syndrome types 1 and 2. Acta Ophthalmol Scand 2006;84:537-544
  23. Seeliger M Pfister M Gendo K Paasch S Apfelstedt-Sylla E Plinkert P Zenner HP Zrenner E: Comparative study of visual, auditory, and olfactory function in Usher syndrome. Graefes Arch Clin Exp Ophthalmol 1999;237:301-307
  24. Tsilou ET Rubin BI Caruso RC Reed GF Pikus A Hejtmancik JF Iwata F Redman JB Kaiser-Kupfer MI: Usher syndrome clinical types I and II: could ocular symptoms and signs differentiate between the two types?. Acta Ophthalmol Scand 2002;80:196-201
  25. Herrera W Aleman TS Cideciyan AV Roman AJ Banin E Ben-Yosef T Gardner LM Sumaroka A Windsor EA Schwartz SB Stone EM Liu XZ Kimberling WJ Jacobson SG: Retinal disease in Usher syndrome III caused by mutations in the clarin-1 gene. Invest Ophthalmol Vis Sci 2008;49:2651-2660
  26. Pennings RJ Huygen PL Orten DJ Wagenaar M van Aarem A Kremer H Kimberling WJ Cremers CW Deutman AF: Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a. Acta Ophthalmol Scand 2004;82:131-139
  27. Plantinga RF Pennings RJ Huygen PL Sankila EM Tuppurainen K Kleemola L Cremers CW Deutman AF: Visual impairment in Finnish Usher syndrome type III. Acta Ophthalmol Scand 2006;84:36-41
  28. Sandberg MA Rosner B Weigel-DiFranco C McGee TL Dryja TP Berson EL: Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene. Invest Ophthalmol Vis Sci 2008;49:5532-5539
  29. Schwartz SB Aleman TS Cideciyan AV Windsor EA Sumaroka A Roman AJ Rane T Smilko EE Bennett J Stone EM Kimberling WJ Liu XZ Jacobson SG: Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. Invest Ophthalmol Vis Sci 2005;46:734-743
  30. Walia S Fishman GA Hajali M: Prevalence of cystic macular lesions in patients with Usher II syndrome. Eye (Lond) 2009;23:1206-1209
  31. Flores-Guevara R Renault F Loundon N Marlin S Pelosse B Momtchilova M Auzoux-Cheve M Vermersch AI Richard P: Usher syndrome type 1: early detection of electroretinographic changes. Eur J Paediatr Neurol 2009;13:505-507
  32. Baux D Faugere V Larrieu L Le Guedard-Mereuze S Hamroun D Beroud C Malcolm S Claustres M Roux AF: UMD-USHbases: a comprehensive set of databases to record and analyse pathogenic mutations and unclassified variants in seven Usher syndrome causing genes. Hum Mutat 2008;29:E76-E87
  33. Ahmed ZM Goodyear R Riazuddin S Lagziel A Legan PK Behra M Burgess SM Lilley KS Wilcox ER Griffith AJ Frolenkov GI Belyantseva IA Richardson GP Friedman TB: The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15. J Neurosci 2006;26:7022-7034
  34. Kazmierczak P Sakaguchi H Tokita J Wilson-Kubalek EM Milligan RA Muller U Kachar B: Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature 2007;449:87-91
  35. van Wijk E Kersten FF Kartono A Mans DA Brandwijk K Letteboer SJ Peters TA Marker T Yan X Cremers CW Cremers FR Wolfram U Roepman R Kremer H: Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein. Hum Mol Genet 2009;18:51-64
  36. Williams DS: Usher syndrome: animal models, retinal function of Usher proteins, and prospects for gene therapy. Vision Res 2008;48:433-441
  37. Bork JM Peters LM Riazuddin S, et al: Usher syndrome 1D and non-syndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet 2001;68:26-37
  38. Riazuddin S Nazli S Ahmed ZM Yang Y Zulfiqar F Shaikh RS Zafar AU Khan SN Sabar F Javid FT Wilcox ER Tsilou E Boger ET Sellers JR Belyantseva IA Friedman TB: Mutation spectrum of MYO7A and evaluation of a novel non-syndromic deafness DFNB2 allele with residual function. Hum Mutat 2008;29:502-511
  39. Schultz JM Yang Y Caride AJ Filoteo AG Penheiter AR Lagziel A Morell RJ Mohiddin SA Fananapazir L Madeo AC Penniston JT Griffith AJ: Modification of human hearing loss by plasma-membrane calcium pump PMCA2. N Engl J Med 2005;352:1557-1564
  40. Liu X Bulgakov OV Darrow KN Pawlyk B Adamian M Liberman MC Li T: Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci USA 2007;104:4413-4418
  41. Gibbs D Kitamoto J Williams DS: Abnormal phagocytosis by retinal pigmented epithelium that lacks myosin VIIa, the Usher syndrome 1B protein. Proc Natl Acad Sci USA 2003;100:6481-6486
  42. Johnson KR Gagnon LH Webb LS Peters LL Hawes NL Chang B Zheng QY: Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene. Hum Mol Genet 2003;12:3075-3086
  43. Haywood-Watson RJ 2nd Ahmed ZM Kjellstrom S Bush RA Takada Y Hampton LL Battey JF Sieving PA Friedman TB: Ames Waltzer deaf mice have reduced electroretinogram amplitudes and complex alternative splicing of Pcdh15 transcripts. Invest Ophthalmol Vis Sci 2006;47:3074-3084
  44. Jacobson SG Cideciyan AV Aleman TS Sumaroka A Roman AJ Gardner LM Prosser HM Mishra M Bech-Hansen NT Herrera W Schwartz SB Liu XZ Kimberling WJ Steel KP Williams DS: Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism. Hum Mol Genet 2008;17:2405-2415
  45. Nudelman I Rebibo-Sabbah A Cherniavsky M Belakhov V Hainrichson M Chen F Schacht J Pilch DS Ben-Yosef T Baasov T: Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J Med Chem 2009;52:2836-2845
  46. Rebibo-Sabbah A Nudelman I Ahmed ZM Baasov T Ben-Yosef T: In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome. Hum Genet 2007;122:373-381
  47. Ebermann I Lopez I Bitner-Glindzicz M Brown C Koenekoop RK Bolz HJ: Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1C gene provides the first genetic link with the Acadian population. Genome Biol 2007;8:R47
  48. Ben-Yosef T Ness SL Madeo AC Bar-Lev A Wolfman JH Ahmed ZM Desnick RJ Willner JP Avraham KB Ostrer H Oddoux C Griffith AJ Friedman TB: A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome. N Engl J Med 2003;348:1664-1670
  49. Dreyer B Tranebjaerg L Brox V Rosenberg T Moller C Beneyto M Weston MD Kimberling WJ Cremers CW Liu XZ Nilssen O: A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. Am J Hum Genet 2001;69:228-234
  50. Fields RR Zhou G Huang D Davis JR Moller C Jacobson SG Kimberling WJ Sumegi J: Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutations. Am J Hum Genet 2002;71:607-617

Pay-per-View Options
Direct payment This item at the regular price: USD 33.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 23.00