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Disease Database

Usher Syndrome

Recent update from: 24.03.2010

This site is maintained and edited by
Dr. rer. medic. Markus Preising, Dipl.Biol.
Laboratory of Molecular Ophthalmology
Department of Opthalmology
Justus-Liebig-University, Giessen, Germany
Head: Prof. Dr. med. Birgit Lorenz

Disease Gene locus MIM Gene Gene MIM MoI Assignment

Linked Marker [cM] Remarks References
Sensorineural Deafness with RP
601815 MTTS2 590085 mt

  • Irish family ZMK-92
  • Link(28)
    type 1, digenic USH1 276900 PCDH15, CDH23 605514,605516 digenic 10q11.2-22

    type 1a USH1A 276900

    ar 14q32

    D14S51- D14S78- D14S13- D14S260, D14S250, D14S292
  • French from Poitou
  • Link(16)
    type 1b USH1B 276903 MyoVIIa 600060 ar 11q13.5

  • MyoVIIa is expressed in RPE and photoreceptors in adult retina
  • RP of USH1b results from a primary rod-cone defect
  • Link(2)
    type 1c USH1C 276904 Harmonin 605242 ar 11p14.3

    D11S861- D11S899
    D11S861- D11S419-(D1S397- D11S902- D11S921- D11S1890- D11S1888(<680 kb))- D11S1310- D11S899- D11S928
  • French Acadian of Louisiana
  • 1 Lebanese family
  • Indian family (DFNB18) => postulate of allelity with USH1c
  • Link(5)
    type 1d USH1D 601067 CDH23 605516 ar 10q21-22

    D10S529- [D10S535- D10S1737]- D10S188- [D10S1432, 152N13aat]- D10S218- [D10S1694- D10S1650]- D10S195- D10S202- D10S69-D10S219- D10S201- D10S551- D10S573 [15]
  • Moroccan and Pakistani families
  • Allelic to DFNB12
  • Link(16)
    type 1e USH1E 602097

    ar 21q21

    D21S1905- D21S1922- D21S1884- D21S1257- D21S1914- D21S265- D21S1896- D21S1258- D21S1916- D21S1913 [15]
    type 1f USH1F 602083 PCDH15 605514 ar 10q11.2-21

    D10S199- D10S596 [15], D10S193, D10S1791, D10S220, D10S1790
  • Pooled DNA PCR
  • Hutterite Brethren
  • Indian
  • Link(4)
    type 1g USH1G 606943 SANS 607696 ar 17q24-25

    D17S949- D17S1350- DFNA26- [D17S1351- D17S1831- D17S1352- D17S1807- D17S1839- D17S1603- D17S785- D17S1806 23]- DFNA20- D17S1830- D17S928
  • Palestinian
  • profound hearing loss
  • vestibular dysfunction
  • inside the interval of a.d. hearing loss DFN20 and DFN26
  • Link(31)
    type 1h USH1H 612632

    ar 15q22-q23

    [D15S988 - ZA909/910 - ZA840/841- ZA856/857 - D15S9777 - D15S980 - D15S818 - D15S973 - D15S1027 - D15S1005 4,92 cM]
    type 2a USH2A 276901 Usherin 608400 ar 1q41

    D1S2646/ D1S2629- DS2827- AFM268ZD1, cen- D1S505- D1S425- D1S217- D1S556- D1S237- [1 D1S474- EB1- EB2- KB6- AFM144XF2]- KB1- KB4- D1S229- D1S490- D1S227-TGFb2- D1S439-tel
  • 9 Lebanese families
  • Link(9)
    type 2b USH2B 276905 SLC4A7 603353 ar 3p24.2-23

  • Tunisian
  • Consanguineous
  • Link(6)
    type 2c USH2C 605472 VLGR1 602851 ar 5q14.3-21.3

    D5S617, D5S484, D5S505, D5S485
  • Screen of 10 linked families and 156 USH2 patients excluded from USH2A
  • Link(32)
    type 2 d USH2D, DFNB31 611383 Whirlin 607928 ar 9q32-q34

    D9S1856 - [D9S289 - D9S1824 - D9S1776 - D9S1682 - D9S1881 15 cM]
    type 3 USH3 276902 Clarin-1 606397 ar 3q21-25

    D3S1299-[1] TW250376- 25B8CA2- 25B8CA1- USH3- 107G19CA7- RSNP2- TSNP1- D3S3625- D3S1594- D3S1279- D3S1308 [5], D3S555, D3S1279, D3S1280
  • Finish and Italian
  • Y100X is the predominant Finish USH mutation
  • (23)
    MoI = Mode of Inheritance: a: autosomal, ad: autosomal dominant, ar: autosomal recessive, xl: x-linked, mt: mitochondrial


    1. Adato,A., Vreugde,S., Joensuu,T., Avidan,N., Hamalainen,R., Belenkiy,O., Olender,T., Bonne-Tamir,B., Ben Asher,E., Espinos,C., Millan,J.M., Lehesjoki,A.E., Flannery,J.G., Avraham,K.B., Pietrokovski,S., Sankila,E.M., Beckmann,J.S., and Lancet,D. USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses. 2002; Eur.J.Hum.Genet. 10: 339-350.
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    2. Adato,A., Weil,D., Kalinski,H., Pelor,Y., Ayadi,H., Petit,C., Korostishevsky,M., and Bonnetamir,B. Mutation Profile Of All 49 Exons Of The Human Myosin VIIA Gene, And Haplotype Analysis, In Usher 1b Families From Diverse Origins. 1997; Am.J.Hum.Genet. 61: 813-821.
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    3. Ahmed,Z.M., Riazuddin,S., Khan,S.N., Friedman,P.L., Riazuddin,S., and Friedman,T.B. USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23. 2009; Clin Genet. 75: 86-91.
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    4. Alagramam,K.N., Yuan,H., Kuehn,M.H., Murcia,C.L., Wayne,S., Srisailpathy,C.R., Lowry,R.B., Knaus,R., Van Laer,L., Bernier,F.P., Schwartz,S., Lee,C., Morton,C.C., Mullins,R.F., Ramesh,A., Van Camp,G., Hagemen,G.S., Woychik,R.P., and Smith,R.J. Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. 2001; Hum.Mol.Genet. 10: 1709-1718.
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    5. Astuto,L.M., Weston,M.D., Carney,C.A., Hoover,D.M., Cremers,C.W., Wagenaar,M., Moller,C., Smith,R.J., Pieke-Dahl,S., Greenberg,J., Ramesar,R., Jacobson,S.G., Ayuso,C., Heckenlively,J.R., Tamayo,M., Gorin,M.B., Reardon,W., and Kimberling,W.J. Genetic Heterogeneity of Usher Syndrome: Analysis of 151 Families with Usher Type I. 2000; Am.J.Hum.Genet. 67: 1569-1574.
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    6. Bok,D., Galbraith,G., Lopez,I., Woodruff,M., Nusinowitz,S., BeltrandelRio,H., Huang,W., Zhao,S., Geske,R., Montgomery,C., Van,S., I, Friddle,C., Platt,K., Sparks,M.J., Pushkin,A., Abuladze,N., Ishiyama,A., Dukkipati,R., Liu,W., and Kurtz,I. Blindness and auditory impairment caused by loss of the sodium bicarbonate cotransporter NBC3. 2003; Nat.Genet. 34: 313-319.
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    7. Bork,J.M., Peters,L.M., Riazuddin,S., Bernstein,S.L., Ahmed,Z.M., Ness,S.L., Polomeno,R., Ramesh,A., Schloss,M., Srisailpathy,C.R., Wayne,S., Bellman,S., Desmukh,D., Ahmed,Z., Khan,S.N., Kaloustian,V.M., Li,X.C., Lalwani,A., Riazuddin,S., Bitner-Glindzicz,M., Nance,W.E., Liu,X.Z., Wistow,G., Smith,R.J., Griffith,A.J., Wilcox,E.R., Friedman,T.B., and Morell,R.J. Usher Syndrome 1D and Nonsyndromic Autosomal Recessive Deafness DFNB12 Are Caused by Allelic Mutations of the Novel Cadherin-Like Gene CDH23. 2001; Am.J.Hum.Genet. 68: 26-37.
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    8. Chaib,H., Kaplan,J., Gerber,S., Vincent,C., Ayadi,H., Slim,R., Munnich,A., Weissenbach,J., and Petit,C. A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome 21q21 A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome 21q21. 1997; Hum.Mol.Genet. 6: 27-31.
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    9. Cremers,F.P.M., Molloy,C.M., van de Pol,D.J.R., van den Hurk,J.A.J.M., Bach,I., van Kessel,A.H.M.G., Ropers,H.H., Cremers,F.P., van de Pol,D.J., van den Hurk,J.A., and Geurts van Kessel,A.H. An autosomal homologue of the choroideremia gene colocalizes with the Usher syndrome type II locus on the distal part of chromosome 1q. 1992; Hum.Mol.Genet. 1: 71-75.
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    10. De Angelis,M.M., Doucet,J.P., Drury,S., Sherry,S.T., Robichaux,M.B., Den,Z., Pelias,M.Z., Ditta,G.M., Keats,B.J., Deininger,P.L., and Batzer,M.A. Assembly of a high-resolution map of the Acadian Usher syndrome region and localization of the nuclear EF-hand acidic gene. 1998; Biochim.Biophys.Acta. 1407: 84-91.
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    11. Ebermann,I., Koenekoop,R.K., Lopez,I., Bou-Khzam,L., Pigeon,R., and Bolz,H.J. An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians. 2009; Eur.J.Hum.Genet. 17: 80-84.
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    12. Ebermann,I., Scholl,H.P., Charbel,I.P., Becirovic,E., Lamprecht,J., Jurklies,B., Millan,J.M., Aller,E., Mitter,D., and Bolz,H. A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss. 2007; Hum.Genet. 121: 203-211.
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    13. El Amraoui,A., Sahly,I., Picaud,S., Sahel,J., Abitbol,M., and Petit,C. Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. 1996; Hum.Mol.Genet. 5: 1171-1178.
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    14. Espinos,C., Najera,C., Millan,J.M., Ayuso,C., Baiget,M., Perez Garrigues,H., Rodrigo,O., Vilela,C., and Beneyto,M. Linkage analysis in Usher syndrome type I (USH1) families from Spain. 1998; J.Med.Genet. 35: 391-398.
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    15. Eudy,J.D., Weston,M.D., Yao,S., Hoover,D.M., Rehm,H.L., Ma Edmonds,M., Yan,D., Ahmad,I., Cheng,J.J., Ayuso,C., Cremers,C., Davenport,S., Moller,C., Talmadge,C.B., Beisel,K.W., Tamayo,M., Morton,C.C., Swaroop,A., Kimberling,W.J., and Sumegi,J. Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. 1998; Science. 280: 1753-1757.
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    16. Gerber,S., Larget Piet,D., Rozet,J.M., Bonneau,D., Mathieu,M., Der Kaloustian,V., Munnich,A., and Kaplan,J. Evidence for a fourth locus in Usher syndrome type I. 1996; J.Med.Genet. 33: 77-79.
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    17. Hejtmancik,J.F., Nestorowicz,A., Li,Y., van Tuinen,P., Smith,H.R., Kaiser-Kupfer,M., Permutt,M.A., and Ayyagari,R. A YAC Contig Encompasing The Usher Syndrome Type 1C Locus On Chromosome 11p14-p15. 1. 1996; Invest.Ophthalmol.Vis.Sci. S656 Goto Top
    18. Hilgert,N., Kahrizi,K., Dieltjens,N., Bazazzadegan,N., Najmabadi,H., Smith,R.J., and Van,C.G. A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family. 2009; J.Med.Genet. 46: 272-276.
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    19. Hmani,M., Ghorbel,A., Boulila-Elgaied,A., Ben Zina,Z., Kammoun,W., Drira,M., Chaabouni,M., Petit,C., and Ayadi,H. A novel locus for Usher syndrome type II, USH2B, maps to chromosome 3 at p23-24.2. 1999; Eur.J.Hum.Genet. 7: 363-367.
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    20. Jain,P.K., Lalwani,A.K., Li,X.C., Singleton,T.L., Smith,T.N., Chen,A., Deshmukh,D., Verma,I.C., Smith,R.J., and Wilcox,E.R. A gene for recessive nonsyndromic sensorineural deafness (DFNB18) maps to the chromosomal region 11p14-p15.1 containing the Usher syndrome type 1C gene. 1998; Genomics. 50: 290-292.
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    21. Joensuu,T., Blanco,G., Pakarinen,L., Sistonen,P., Kaariainen,H., Brown,S., Chapelle,A., and Sankila,E.M. Refined mapping of the Usher syndrome type III locus on chromosome 3, exclusion of candidate genes, and identification of the putative mouse homologous region. 1996; Genomics. 38: 255-263.
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    22. Joensuu,T., Hamalainen,R., Yuan,B., Johnson,C., Tegelberg,S., Gasparini,P., Zelante,L., Pirvola,U., Pakarinen,L., Lehesjoki,A.E., la Chapelle,A., and Sankila,E.M. Mutations in a novel gene with transmembrane domains underlie usher syndrome type 3. 2001; Am.J.Hum.Genet. 69: 673-684.
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    23. Joensuu,T.H., Hämäläinen,R.H., Lehesjoki,A.E., de la Chapelle,A., and Sankila,E.M. Refined physical and partial transcript map of the Usher syndrome type III region. 1998; Am.J.Hum.Genet. 63: A250 Goto Top
    24. Kaplan,J., Pelet,A., Martin,C., Delrieu,O., Ayme,S., Bonneau,D., Briard,M.L., Hanauer,A., Larget Piet,L., and Lefrancois,P. Phenotype-genotype correlations in X linked retinitis pigmentosa. 1992; J.Med.Genet. 29: 615-623.
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    25. Keats,B.J., Nouri,N., Pelias,M.Z., Deininger,P.L., and Litt,M. Tightly linked flanking microsatellite markers for the Usher syndrome type I locus on the short arm of chromosome 11. 1994; Am.J.Hum.Genet. 54: 681-686.
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    26. Kimberling,W.J., Aarem van,A., Sumegi,J., Connoly,C., Weston,M.D., Cremers,C.W.R.J., Suy,P.S., Martini,A., Milana,M., Tamayo,M.L., Bernal,J., Greenberg,J., Ayuso,C., Moller,C., van Aarem,A., Cremers,C.W., Ing,P.S., Connolly,C., and Milani,M. Gene mapping of Usher Syndrome Type IIa: Localisation of the gene to a 2.1 cM segment on chromosome 1q41. 1995; Am.J.Hum.Genet. 56: 216-223.
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    27. Levy,G., Leviacobas,F., Blanchard,S., Gerber,S., Largetpiet,D., Chenal,V., Liu,X.Z., Newton,V., Steel,K.P., Brown,S.D.M., Munnich,A., Kaplan,J., Petit,C., Weil,D., Levi Acobas,F., Larget Piet,D., and Brown,S.D. Myosin VIIa Gene: Heterogeneity Of The Mutations Responsible For Usher Syndrome Type Ib. 1997; Hum.Mol.Genet. 6: 111-116.
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    28. Mansergh,F.C., Millington-Ward,S., Kennan,A., Kiang,A.S., Humphries,M., Farrar,G.J., Humphries,P., and Kenna,P.F. Retinitis Pigmentosa and Progressive Sensorineural Hearing Loss Caused by a C12258A Mutation in the Mitochondrial MTTS2 Gene. 1999; Am.J.Hum.Genet. 64: 971-985.
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    29. Mburu,P., Mustapha,M., Varela,A., Weil,D., El-Amraoui,A., Holme,R.H., Rump,A., Hardisty,R.E., Blanchard,S., Coimbra,R.S., Perfettini,I., Parkinson,N., Mallon,A.M., Glenister,P., Rogers,M.J., Paige,A.J., Moir,L., Clay,J., Rosenthal,A., Liu,X.Z., Blanco,G., Steel,K.P., Petit,C., and Brown,S.D. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. 2003; Nat.Genet. 34: 421-428.
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    30. Mustapha,M., Chouery,E., Chardenoux,S., Naboulsi,M., Paronnaud,J., Lemainque,A., Megarbane,A., Loiselet,J., Weil,D., Lathrop,M., and Petit,C. DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32-34. 2002; Eur.J.Hum.Genet. 10: 210-212.
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    31. Mustapha,M., Chouery,E., Torchard-Pagnez,D., Nouaille,S., Khrais,A., Sayegh,F.N., Megarbane,A., Loiselet,J., Lathrop,M., Petit,C., and Weil,D. A novel locus for Usher syndrome type I, USH1G, maps to chromosome 17q24-25. 2002; Hum.Genet. 110: 348-350.
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    32. Pieke-Dahl,S., Moller,C.G., Kelley,P.M., Astuto,L.M., Cremers,C.W., Gorin,M.B., and Kimberling,W.J. Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q. 2000; J.Med.Genet. 37: 256-262.
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    33. Sankila,E.M., Pakarinen,L., Kaariainen,H., Aittomaki,K., Karjalainen,S., Sistonen,P., and de la Chapelle,A. Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q. 1995; Hum.Mol.Genet. 4: 93-98.
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    34. Saouda,M., Mansour,A., Bou Moglabey,Y., El Zir,E., Mustapha,M., Chaib,H., Nehme,A., Megarbane,A., Loiselet,J., Petit,C., and Slim,R. The Usher syndrome in the Lebanese population and further refinement of the USH2A candidate region. 1998; Hum.Genet. 103: 193-198.
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    35. Slim,R., Mansour,A., Bou Moglabey,Y., El Zir,E., Mustapha,M., and Loiselet,J. The Usher syndrome in the Lebanese population: evidence of further genetic heterogeneity in type I and III. 1998; Am.J.Hum.Genet. 63: A309 Goto Top
    36. Smith,J.C., Webb,T., Pembrey,M.E., Nichols,M., and Malcolm,S. Maternal origin of deletion 15q11-13 in 25/25 cases of Angelman syndrome. 1992; Hum.Genet. 88: 376-378.
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    37. Smith,R.J., Lee,E.C., Kimberling,W.J., Daiger,S.P., Pelias,M.Z., Keats,B.J.B., Jay,M., Bird,A.C., Reardon,W., Guest,M., Ayyagari,R., Hejtmancik,J.F., Keats,B.J., and Bird,A. Localization of two genes for Usher syndrome type I to chromosome 11. 1992; Genomics. 14: 995-1002.
      Link Goto Top
    38. Sumegi,J., Wang,J.Y., Zhen,D.K., Eudy,J.D., Talmadge,C.B., Li,B.F., Berglund,P., Weston,M.D., Yao,S.F., Ma Edmonds,M., Overbeck,L., Kelley,P.M., Zabarovsky,E., Uzvolgyi,E., Stanbridge,E.J., Klein,G., and Kimberling,W.J. The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type IIa (USH2A) gene in 1q41. 1996; Genomics. 35: 79-86.
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    39. Verpy,E., Leibovici,M., Zwaenepoel,I., Liu,X.Z., Gal,A., Salem,N., Mansour,A., Blanchard,S., Kobayashi,I., Keats,B.J., Slim,R., and Petit,C. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. 2000; Nat.Genet. 26: 51-55.
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    40. Wayne,S., Der Kaloustian,V.M., Schloss,M., Polomeno,R., Scott,D.A., Hejtmancik,J.F., Sheffield,V.C., and Smith,R.J. Localization of the Usher syndrome type ID gene (USH1D) to chromosome 10. 1996; Hum.Mol.Genet. 5: 1689-1692.
      Link Goto Top
    41. Wayne,S., Lowry,R.B., Mcleod,D.R., Knaus,R., Farr,C., and Smith,R.J.H. Localization of the Usher syndrome type 1F (USH1F) to chromosome 10. 1997; Am.J.Hum.Genet. 61: A300 Goto Top
    42. Weil,D., Blanchard,S., Kaplan,J., Guilford,P., Gibson,F., Walsh,J., Mburu,P., Varela,A., Levilliers,J., Weston,M.D., Kelley,P.M., Kimberling,W.J., Wagenaar,M., Levi Acobas,F., Larget-Piet,D., Munnich,A., Steel,K.P., Brown,S.D.M., and Petit,C. Defective myosin VIIA gene responsible for Usher syndrome type 1B. 1995; Nature. 374: 60-61.
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    43. Weil,D., El Amraoui,A., Masmoudi,S., Mustapha,M., Kikkawa,Y., Laine,S., Delmaghani,S., Adato,A., Nadifi,S., Zina,Z.B., Hamel,C., Gal,A., Ayadi,H., Yonekawa,H., and Petit,C. Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. 2003; Hum.Mol.Genet. 12: 463-471.
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    44. Weil,D., Kussel,P., Blanchard,S., Levy,G., Levi Acobas,F., Drira,M., Ayadi,H., and Petit,C. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. 1997; Nat.Genet. 16: 191-193.
      Link Goto Top
    45. Weston,M.D., Luijendijk,M.W., Humphrey,K.D., Moller,C., and Kimberling,W.J. Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II. 2004; Am.J.Hum.Genet. 74: 357-366.
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    46. Zheng,Q.Y., Yan,D., Ouyang,X.M., Du,L.L., Yu,H., Chang,B., Johnson,K.R., and Liu,X.Z. Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans. 2005; Hum.Mol.Genet. 14: 103-111.
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