Genetik und molekulare Grundlagen der nicht-syndromalen Taubheit

  • Christian Kubisch
  • Hanno Bolz
  • Andreas Gal
Part of the Handbuch der Molekularen Medizin book series (HDBMOLEK, volume 7)


Störungen des Hörens im Sinn einer (meist progredienten) Schwerhörigkeit oder Taubheit stellen den hßufigsten primßr sensorischen Defekt des Menschen dar. Die Auswirkungen der Taubheit sind sowohl für das betroffene Individuum und sein nßheres Umfeld als auch für die Gesellschaft bedeutend. Der Erkrankte selbst ist in der Kommunikationsfßhigkeit mit seiner Umwelt und somit in seinem sozialen Interaktionsgefüge beeintrßchtigt. Dies ist umso ausgeprßgter, je stßrker die Erkrankung mit einer Einschrßnkung der Sprache ntwicklung oder des verbalen Sprachvermögens einhergeht. Für die Gesellschaft (und hier insbesondere für das Gesundheitswesen) bedeutet Taubheit ein großes volkswirtschaftliches Problem.


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  1. Anderson S., Bankier A.T., Barrell B.G. et al. (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465PubMedGoogle Scholar
  2. Arden G.B., Fox B. (1979) Increased incidence of abnormal nasal cilia in patients with retinitis pigmentosa. Nature 279:534–536PubMedGoogle Scholar
  3. Avraham K.B., Hasson T., Steel K.P. et al. (1995) The mouse Snell’s waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells. Nat Genet 11:369–375PubMedGoogle Scholar
  4. Avraham K.B., Hasson T., Sobe T. et al. (1997) Characterization of unconventional MY06, the human homologue of the gene responsible for deafness in Snell’s waltzer mice. Hum Mol Genet 6:1225–1231PubMedGoogle Scholar
  5. Ballinger S.W., Shoffner J.M., Hedaya E.V. et al. (1992) Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1:11–15PubMedGoogle Scholar
  6. Barhanin J., Lesage F., Guillemare E., Fink M., Lazdunski M., Romey G. (1996) K(V)LQT1 and 1sK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384:78–80PubMedGoogle Scholar
  7. Barker D.F., Hostikka S.L., Zhou J. et al. (1990) Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science 248:1224–1227PubMedGoogle Scholar
  8. Barrong S.D., Chaitin M.H., Fliesler S.J., Possin D.E., Jacobson S.G., Milam A.H. (1992) Ultrastructure of connecting cilia in different forms of retinitis pigmentosa. Arch Ophthalmol 110:706–710PubMedGoogle Scholar
  9. Bonne G., Carrier L., Bercovici J. et al. (1995) Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophie cardiomyopathy. Nat Genet 11:438–440PubMedGoogle Scholar
  10. Bonneau D., Raymond F., Kremer C., Klossek J.M., Kaplan J., Patte F. (1993) Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers. J Med Genet 30:253–254PubMedGoogle Scholar
  11. Brunner H.G., Bennekom A. van, Lambermon E.M. et al. (1988) The gene for X-linked progressive mixed deafness with perilymphatie gusher during stapes surgery (DFN3) is linked to PGK. Hum Genet 80:337–340PubMedGoogle Scholar
  12. Bykhovskaya Y., Shohat M., Ehrenman K. et al. (1998) Evidence for complex nuclear inheritance in a pedigree with nonsyndromic deafness due to a homoplasmic mitochondrial mutation. Am J Med Genet 77:421–426PubMedGoogle Scholar
  13. Capecchi M.R. (1989) Altering the genome by homologous recombination. Science 244:1288–1292PubMedGoogle Scholar
  14. Carrasquillo M.M., Zlotogora J., Barges S., Chakravarti A. (1997) Two different connexin 26 mutations in an inbred kindred segregating non-syndromie recessive deafness: implications for genetic studies in isolated populations. Hum Mol Genet 6:2163–2172PubMedGoogle Scholar
  15. Castrillon D.H., Wasserman S.A. (1994) Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development 120:3367–3377PubMedGoogle Scholar
  16. Charpentier F., Merot J., Riochet D., Le Marec H., Escande D. (1998) Adult KCNE1-knockout mice exhibit a mild cardiac cellular phenotype. Biochem Biophys Res Commun 251:806–810PubMedGoogle Scholar
  17. Chouabe C., Neyroud N., Guicheney P., Lazdunski M., Romey G., Barhanin J. (1997) Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J 16:5472–5479PubMedGoogle Scholar
  18. Colville D.J., Savige J. (1997) Alport syndrome. A review of the ocular manifestations. Ophthalmic Genet 18:161–173PubMedGoogle Scholar
  19. Corwin J.T., Oberholtzer J.C. (1997) Fish n’ chicks: model recipes for hair-cell regeneration? Neuron 19:951–954PubMedGoogle Scholar
  20. Coucke P., Van Camp G., Djoyodiharjo B. et al. (1994) Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families. N Engl J Med 331:425–431PubMedGoogle Scholar
  21. Crozet F, el Amraoui A., Blanchard S. et al. (1997) Cloning of the genes encoding two murine and human cochlear unconventional type I myosins. Genomics 40:332–341PubMedGoogle Scholar
  22. Davis A.C. (1989) The prevalence of hearing impairment and reported hearing disability among adults in Great Britain. Int J Epidemiol 18:911–917PubMedGoogle Scholar
  23. De Kok Y.J., Maarel S.M. van der, Bitner-Glindziez M et al. (1995) Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science 267:685–688PubMedGoogle Scholar
  24. Denoyelle F., Weil D., Maw M.A. et al. (1997) Prelingual deafness: high prevalence of a 30deiG mutation in the connexin 26 gene. Hum Mol Genet 6:2173–2177PubMedGoogle Scholar
  25. Denoyelle F., Lina-Granade G., Plauchu H. et al. (1998) Connexin 26 gene linked to a dominant deafness. Nature 393:319–320PubMedGoogle Scholar
  26. Drici M.D., Arrighi I., Chouabe C. et al. (1998) Involvement of IsK-associated K+ channel in heart rate control of repolarization in a murine engineered model of Jervell and Lange-Nielsen syndrome. Circ Res 83:95–102PubMedGoogle Scholar
  27. El-Amraoui A., Sahly I, Picaud S., Sahel J., Abitbol M., Petit C. (1996) Human Usher 1B/mouse shaker-1: the retinal pheno type discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. Hum Mol Genet 5:1171–1178PubMedGoogle Scholar
  28. Erkman L., McEvilly R.J., Luo L. et al. (1996) Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development. Nature 381:603–606PubMedGoogle Scholar
  29. Estivill X., Fortina P., Surrey S. et al. (1998a) Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet 351:394–398PubMedGoogle Scholar
  30. Estivill X., Govea N., Barcelo E. et al. (1998 b) Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides. Am J Hum Genet 62:27–35PubMedGoogle Scholar
  31. Eudy J.D., Weston M.D., Yao S. et al. (1998) Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science 280:1753–1757PubMedGoogle Scholar
  32. Everett L.A., Glaser B., Beck J.C. et al. (1997) Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 17:411–422PubMedGoogle Scholar
  33. Fields S., Sternglanz R. (1994) The two-hybrid system: an assay for protein-protein interactions. Trends Genet 10:286–292PubMedGoogle Scholar
  34. Fischel-Ghodsian N., Prezant T.R., Fournier P., Stewart I.A., Maw M. (1995) Mitochondrial mutation associated with nonsyndromie deafness. Am J Otolaryngol 16:403–408PubMedGoogle Scholar
  35. Flinter F. (1997) Alport’s syndrome. J Med Genet 34:326–330PubMedGoogle Scholar
  36. Friedmann I., Fraser G.R., Froggatt P. (1966) Pathology of the ear in the cardioauditory syndrome of Jervell and Lange-Nielsen (recessive deafness with electrocardiographic abnormalities). J Laryngol Otol 80:451–470PubMedGoogle Scholar
  37. Friedman T.B., Liang Y., Weber J.L. et al. (1995) A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat Genet 9:86–91PubMedGoogle Scholar
  38. Gabriel H.D., Jung D., Butzler C. et al. (1998) Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice. J Cell Biol 140:1453–1461PubMedGoogle Scholar
  39. Geisterfer-Lowrance A.A., Kass S., Tanigawa G. et al. (1990) A molecular basis for familial hypertrophie cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 62:999–1006PubMedGoogle Scholar
  40. Gibson F., Walsh J., Mburu P. et al. (1995) A type VII myosin encoded by the mouse deafness gene shaker-1. Nature 374:62–64PubMedGoogle Scholar
  41. Giles R.E., Blanc H., Cann H.M., Wallace D.C. (1980) Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 77:6715–6719Google Scholar
  42. Gillespie P.G., Corey D.P. (1997) Myosin and adaptation by hair cells. Neuron 19:955–958PubMedGoogle Scholar
  43. Gorlin R.J., Toriello H.V., Cohen M.M. (1995) Hereditary hearing loss and its syndromes. Oxford University Press, OxfordGoogle Scholar
  44. Gravel M., Melancon P., Brakier-Gingras L. (1987) Cross-linking of streptomycin to the 16 S ribosomal RNA of Escherichia coli. Biochemistry 26:6227–6232PubMedGoogle Scholar
  45. Gray M.W. (1992) The endosymbiont hypothesis revisited. Int Rev Cytol 141:233–357PubMedGoogle Scholar
  46. Guan M.X., Fischel-Ghodsian N., Attardi G. (1996) Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12 S rRNA mutation. Hum Mol Genet 5:963–971PubMedGoogle Scholar
  47. Guan M.X., Enriquez J.A., Fischel-Ghodsian N. et al. (1998) The deafness-associated mitochondrial DNA mutation at positIOn 7445, which affects tRNASer(UCN) precursor processing, has long-range effects on NADH dehydrogenase subunit ND6 gene expression. Mol Cell Biol 18:5868–5879PubMedGoogle Scholar
  48. Guilford P., Ayadi H., Blanchard S. et al. (1994) A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene. Hum Mol Genet 3:989–993PubMedGoogle Scholar
  49. Gurdon J.B., Lane C.D., Woodland H.R., Marbaix G. (1971) Use of frog eggs and oocytes for the study of messenger RNA and its translation in living cells. Nature 233:177–182PubMedGoogle Scholar
  50. Hackney C.M., Furness D.N. (1995) Mechanotransduction in vertebrate hair cells: structure and function of the stereociliary bundle. Am J Physiol 268:C1–13Google Scholar
  51. Hamasaki K., Rando R.R. (1997) Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness. Biochemistry 36:12323–12328PubMedGoogle Scholar
  52. Hasson T., Heintzelman M.B., Santos-Sacchi J., Corey D.P., Mooseker M.S. (1995) Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type IB. Proc Natl Acad Sci USA 92:9815–9819Google Scholar
  53. Hasson T., Skowron J.F., Gilbert D.J. et al. (1996) Mapping of unconventional myosins in mouse and human. Genomics 36:431–439PubMedGoogle Scholar
  54. Hasson T., Gillespie P.G., Garcia J.A. et al. (1997) Unconventional myosins in inner-ear sensory epithelia. J Cell Biol 137:1287–1307PubMedGoogle Scholar
  55. Heller S., Sheane C.A., Javed Z., Hudspeth A.J. (1998) Molecular markers for cell types of the inner ear and candidate genes for hearing disorders. Proc Natl Acad Sci USA 95:11400–11405Google Scholar
  56. Higashi K. (1989) Unique inheritance of streptomycin-induced deafness. Clin Genet 35:433–436PubMedGoogle Scholar
  57. Hornig H., Woolley P., Luhrmann R. (1987) Decoding at the ribosomal A site: antibiotics, misreading and energy of aminoacyl-tRNA binding. Biochimie 69:803–813PubMedGoogle Scholar
  58. Hoth C.F., Milunsky A., Lipsky N., Sheffer R., Clarren S.K., Baldwin C.T. (1993) Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as weil as Waardenburg syndrome type I (WSI). Am J Hum Genet 52:455–462PubMedGoogle Scholar
  59. Hu D.N., Qui W.Q., Wu B.T. et al. (1991) Genetic aspects of antibiotic induced deafness: mitochondrial inheritance. J Med Genet 28:79–83PubMedGoogle Scholar
  60. Hudspeth A. (1997 a) Mechanical amplification of stimuli by hair cells. Curr Opin Neurobiol 7:480–486PubMedGoogle Scholar
  61. Hudspeth A.J. (1997b) How hearing happens. Neuron 19:947–950PubMedGoogle Scholar
  62. Hughes D.C., Legan P.K., Steel K.P., Richardson G.P. (1998) Mapping of the alpha-tectorin gene (TECTA) to mouse chromosome 9 and human chromosome 11: a candidate for human autosomal dominant nonsyndromic deafness. Genomics 48:46–51PubMedGoogle Scholar
  63. Hulander M., Wurst W., Carlsson P., Enerback S. (1998) The winged helix transcription factor FkhlO is required for normal development of the inner ear. Nat Genet 20:374–376PubMedGoogle Scholar
  64. Hunter D.G., Fishman G.A., Mehta R.S., Kretzer F.L. (1986) Abnormal sperm and photoreceptor axonemes in Usher’s syndrome. Arch Ophthalmol 104:385–389PubMedGoogle Scholar
  65. Ikeda K., Morizono T. (1989) Electrochemical profiles for monovalent ions in the stria vascularis: cellular model of ion transport mechanisms. Hear Res 39:279–286PubMedGoogle Scholar
  66. Ingber D.E. (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol 59:575–599PubMedGoogle Scholar
  67. Jacob A.N., Manjunath N.A., Bray-Ward P., Kandpal R.P. (1998) Molecular cloning of a zinc finger gene eZNF from a human inner ear cDNA library, and in situ-expression pattern of its mouse homologue in mouse inner ear. Somat Cell Mol Genet 24:121–129PubMedGoogle Scholar
  68. Jacobs H.T. (1997) Mitochondrial deafness. Ann Med 29:483–491PubMedGoogle Scholar
  69. Janmey P.A. (1998) The cytoskeleton and cell signaling: component localization and mechanical coupling. Physiol Rev 78:763–781PubMedGoogle Scholar
  70. Jervell A., Lange-Nielsen F. (1957) Congenital deaf-mutism, functional heart disease with prolongation of Q-T interval and sudden death. Am Heart J 54:59–68PubMedGoogle Scholar
  71. Johnsonbaugh R.E., Drexler H.G., Light I.J., Sutherland J.M. (1974) Familial occurrence of drug-induced hearing loss. Am J Dis Child 127:245–247PubMedGoogle Scholar
  72. Kalatzis V., Petit C. (1998) The fundamental and medieal impacts of recent progress in research on hereditary hearing loss. Hum Mol Genet 7:1589–1597PubMedGoogle Scholar
  73. Kelley P.M., Harris D.J., Corner B.C. et al. (1998) Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss. Am J Hum Genet 62:792–799PubMedGoogle Scholar
  74. Kelsell D.P., Dunlop J., Stevens H.P. et al. (1997) Connexin 26 mutations in hereditary non-syndromie sensorineural deafness. Nature 387:80–83PubMedGoogle Scholar
  75. Khetarpal U. (1993) Autosomal dominant sensorineural hearing loss. Further temporal bone findings. Arch Otolaryngol Head Neck Surg 119:106–108PubMedGoogle Scholar
  76. Khetarpal U., Schuknecht H.F., Gacek R.R., Holmes L.B. (1991) Autosomal dominant sensorineural hearing loss. Pedigrees, audiologie findings, and temporal bone findings in two kindreds. Arch Otolaryngol Head Neck Surg 117:1032–1042PubMedGoogle Scholar
  77. Kikuchi T., Kimura R.S., Paul D.L., Adams J.C. (1995) Gap junctions in the rat cochlea: immunohistochemieal and ultrastructural analysis. Anat Embryol (Berl) 191:101–118Google Scholar
  78. Kim H.J., Noben-Trauth K., Moreli R.J. (1998) Tectorin-beta (Tectb) maps to mouse chromosome 19. Genomics 53:419–420Google Scholar
  79. Kimberling W.J., Moller C. (1995) clinical and molecular genetics of Usher syndrome. J Am Acad Audiol 6:63–72PubMedGoogle Scholar
  80. Kubisch C., Schroeder B.C., Friedrieh T. et al. (1999) KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 96:437–446PubMedGoogle Scholar
  81. Kuhlbrodt K., Schmidt C., Sock E. et al. (1998) Functional analysis of SoxlO mutations found in human Waardenburg-Hirschsprung patients. J Biol Chem 273:23.033–23038Google Scholar
  82. Kumar N.M., Gilula N.B. (1996) The gap junction communication channel. Cell 84:381–388PubMedGoogle Scholar
  83. Kunst H., Marres H., Van Camp G., Cremers C. (1998) Nonsyndromic autosomal dominant sensorineural hearing loss: a new field of research. Clin Otolaryngol 23:9–17PubMedGoogle Scholar
  84. Legan P.K., Rau A., Keen J.N., Riehardson G.P. (1997) The mouse tectorins. Modular matrix proteins of the inner ear homologous to components of the sperm-egg adhesion system. J Biol Chem 272:8791–8801PubMedGoogle Scholar
  85. Leon P.E., Raventos H., Lynch E., Morrow J., King M.C. (1992) The gene for an inherited form of deafness maps to chromosome 5q31. Proc Natl Acad Sci USA 89:5181–5184PubMedGoogle Scholar
  86. Li X.C., Everett L.A., Lalwani A.K. et al. (1998) A mutation in PDS causes non-syndromie recessive deafness. Nat Genet 18:215–217PubMedGoogle Scholar
  87. Liang Y., Wang A., Probst F.J. et al. (1998) Genetic mapping refines DFNB3 to 17p 11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2. Am J Hum Genet 62:904–915PubMedGoogle Scholar
  88. Liu X.Z., Walsh J., Mburu P. et al. (1997 a) Mutations in the myosin VIIA gene cause non-syndromie recessive deafness. Nat Genet 16:188–190PubMedGoogle Scholar
  89. Liu X.Z., Walsh J., Tamagawa Y. et al. (1997b) Autosomal dominant non-syndromie deafness caused by a mutation in the myosin VIIA gene. Nat Genet 17:268–269PubMedGoogle Scholar
  90. Liu X.Z., Hope C., Walsh J. et al. (1998) Mutations in the myosin VIIA gene cause a wide phenotypie spectrum, including atypieal Usher syndrome. Am J Hum Genet 63:909–912PubMedGoogle Scholar
  91. Loizou P.C. (1999) Introduction to cochlear implants. IEEE Eng Med Biol Mag 18:32–42PubMedGoogle Scholar
  92. Lynch E.D., Lee M.K., Morrow J.E., Welcsh P.L., Leon P.E., King M.C. (1997) Nonsyndromie deafness DFNA1 assoeiated with mutation of a human homolog of the Drosophila gene diaphanous. Science 278:1315–1318PubMedGoogle Scholar
  93. Manolis E.N., Yandavi N., Nadol J.B. Jr et al. (1996) A gene for non-syndromie autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13. Hum Mol Genet 5:1047–1050PubMedGoogle Scholar
  94. Manouvrier S., Rotig A., Hannebique G. et al. (1995) Point mutation of the mitochondrial tRNA(Leu) gene (A 3243 G) in maternally inherited hypertrophie cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness. J Med Genet 32:654–656PubMedGoogle Scholar
  95. Marazita M.L., Ploughman L.M., Rawlings B., Remington E., Arnos K.S., Nance W.E. (1993) Genetic epidemiologieal studies of early-onset deafness in the U.S. school-age population. Am J Med Genet 46:486–491PubMedGoogle Scholar
  96. Marcus D.C., Shen Z. (1994) Slowly activating voltage-dependent K+ conductance is apieal pathway for K+ secretion in vestibular dark cells. Am J Physiol 267:C857–C864PubMedGoogle Scholar
  97. Mermall V., Post P.L., Mooseker M.S. (1998) Unconventional myosins in cell movement, membrane traffic, and signal transduction. Science 279:527–533PubMedGoogle Scholar
  98. Metcalf A.B. (1998) Immunolocalization of myosin Ibeta in the hair cell’s hair bundle. Cell Motil Cytoskeleton 39:159–165PubMedGoogle Scholar
  99. Moazed D., NoHer H.F. (1987) Interaction of antibiotics with functional sites in 16 S ribosomal RNA. Nature 327:389–394PubMedGoogle Scholar
  100. Mochizuki T., Lemmink H.H., Mariyama M. et al. (1994) Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8:77–81PubMedGoogle Scholar
  101. Morell R.J., Kim H.J., Hood L.J. et al. (1998) Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromie recessive deafness. N Engl J Med 339:1500–1505PubMedGoogle Scholar
  102. Morton N.E. (1991) Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 630:16–31PubMedGoogle Scholar
  103. Neyroud N., Tesson F., Denjoy I. et al. (1997) A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet 15:186–189PubMedGoogle Scholar
  104. Petit C. (1996) Genes responsible for human hereditary deafness: symphony of a thousand. Nat Genet 14:385–391PubMedGoogle Scholar
  105. Phizicky E.M., Fields S. (1995) Protein-protein interactions: methods for detection and analysis. Microbiol Rev 59:94–123PubMedGoogle Scholar
  106. Pingault V., Bondurand N., Kuhlbrodt K. et al. (1998) SOX1O mutations in patients with Waardenburg-Hirschsprung disease. Nat Genet 18:171–173PubMedGoogle Scholar
  107. Prezant T.R., Agapian J.V., Bohlman M.C. et al. (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotie-induced and non-syndromic deafness. Nat Genet 4:289–294PubMedGoogle Scholar
  108. Probst F.J., Fridell R.A., Raphael Y. et al. (1998) Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280:1444–1447PubMedGoogle Scholar
  109. Reid F.M., Vernham G.A., Jacobs H.T. (1994) A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness. Hum Mutat 3:243–247PubMedGoogle Scholar
  110. Riehard G., Smith L.E., Bailey R.A. et al. (1998a) Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nat Genet 20:366–369Google Scholar
  111. Richard G., White T.W., Smith L.E. et al. (1998b) Functional defects of Cx26 resulting from a heterozygous missen se mutation in a family with dominant deaf-mutism and palmoplantar keratoderma. Hum Genet 103:393–399PubMedGoogle Scholar
  112. Richardson G.P., Russell I.J., Duance V.C., Bailey A.J. (1987) Polypeptide composition of the mammalian tectorial membrane. Hear Res 25:45–60PubMedGoogle Scholar
  113. Rivolta M.N. (1997) Transcription factors in the ear: molecular switches for development and differentiation. Audiol Neurootol 2:36–49PubMedGoogle Scholar
  114. Robertson N.G., Khetarpal U., Gutierrez-Espeleta G.A., Bieber F.R., Morton C.C. (1994) Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening. Genomics 23:42–50PubMedGoogle Scholar
  115. Robertson N.G., Skvorak A.B., Yin Y. et al. (1997) Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9. Genomics 46:345–354PubMedGoogle Scholar
  116. Robertson N.G., Lu L., Heller S. et al. (1998) Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromie deafness with vestibular dysfunction. Nat Genet 20:299–303PubMedGoogle Scholar
  117. Roden D.M., George A.L. Jr. (1996) The cardiac ion channels: relevance to management of arrhythmias. Annu Rev Med 47:135–148PubMedGoogle Scholar
  118. Ryan A.K., Rosenfeld M.G. (1997) POU domain family values: flexibility, partnerships, and developmental codes. Genes Dev 11:1207–1225PubMedGoogle Scholar
  119. Sahly I., El-Amraoui A., Abitbol M., Petit C., Dufier J.L. (1997) Expression of myosin VIIA during mouse embryogenesis. Anat Embryol (Berl) 196:159–170Google Scholar
  120. Sakagami M., Fukazawa K., Matsunaga T. et al. (1991) Cellular localization of rat Isk protein in the stria vascularis by immunohistochemieal observation. Hear Res 56:168–172PubMedGoogle Scholar
  121. Sanguinetti M.C., Curran M.E., Zou A. et al. (1996) Coassembly of K(V)LQT1 and minK (IsK) pro teins to form cardiac I(Ks) potassium channel. Nature 384:80–83PubMedGoogle Scholar
  122. Schroeder B.C., Kubisch C., Stein V., Jentsch T.J. (1998) Moderate loss of function of cyclie-AMP-modulated KCNQ2/ KCNQ3 K+ channels causes epilepsy. Nature 396:687–690PubMedGoogle Scholar
  123. Schulze-Bahr E., Wang Q., Wedekind H. et al. (1997) KCNEI mutations cause Jervell and Lange-Nielsen syndrome. Nat Genet 17:267–268PubMedGoogle Scholar
  124. Scott D.A., Kraft M.L., Carmi R. et al. (1998) Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromie hearing loss. Hum Mutat 11:387–394PubMedGoogle Scholar
  125. Self T., Mahony M., Fleming J., Walsh J., Brown S.D., Steel K.P. (1998) Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells. Development 125:557–566PubMedGoogle Scholar
  126. Sevior K.B., Hatamochi A., Stewart I.A. et al. (1998) Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness. Am J Med Genet 75:179–185PubMedGoogle Scholar
  127. Shinkawa H., Nadol J.B. Jr (1986) Histopathology of the inner ear in Usher’s syndrome as observed by light and electron microscopy. Ann Otol Rhinol Laryngol 95:313–318PubMedGoogle Scholar
  128. Simon A.M., Goodenough D.A. (1998) Diverse functions of vertebrate gap junctions. Trends Cell Biol 8:477–482PubMedGoogle Scholar
  129. Simon D.K., Johns D.R. (1999) Mitochondrial dis orders: clinical and genetic features. Annu Rev Med 50:111–127PubMedGoogle Scholar
  130. Smith R.J., Berlin C.I., Hejtmancik J.F. et al. (1994) Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet 50:32–38PubMedGoogle Scholar
  131. Spieer S.S., Schulte B.A. (1998) Evidence for a medial K+ recycling pathway from inner hair cells. Hear Res 118:1–12Google Scholar
  132. Splawski I., Tristani-Firouzi M., Lehmann M.H., Sanguinetti M.C., Keating M.T. (1997) Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet 17:338–340PubMedGoogle Scholar
  133. Staecker H., Van De Water T.R. (1998) Factors controlling hair-cell regeneration/repair in the inner ear. Curr Opin Neurobiol 8:480–487PubMedGoogle Scholar
  134. Steel K.P. (1995) Inherited hearing defects in mice. Annu Rev Genet 29:675–701PubMedGoogle Scholar
  135. Street V.A., McKee-Johnson J.W., Fonseca R.C., Tempel B.L., Noben-Trauth K. (1998) Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet 19:390–394PubMedGoogle Scholar
  136. Sunose H., Ikeda K., Suzuki M., Takasaka T. (1994) Voltage-activated K channel in luminal membrane of marginal cells of stria vascularis dissected from guinea pig. Hear Res 80:86–92PubMedGoogle Scholar
  137. Swenson K.I., Jordan J.R., Beyer E.C., Paul D.L. (1989) Formation of gap junctions by expression of connexins in Xenopus oocyte pairs. Cell 57:145–155PubMedGoogle Scholar
  138. Takumi T., Ohkubo H., Nakanishi S. (1988) Cloning of a membrane protein that induces a slow voltage-gated potassium current. Science 242:1042–1045PubMedGoogle Scholar
  139. Tamagawa Y., Kitamura K., Ishida T. et al. (1996) A gene for a dominant form of non-syndromic sensorineural deafness (DFNA11) maps within the region containing the DFNB2 recessive deafness gene. Hum Mol Genet 5:849–852PubMedGoogle Scholar
  140. Tassabehji M., Read A.P., Newton V.E. et al. (1992) Waardenburg’s syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 355:635–636PubMedGoogle Scholar
  141. Tassabehji M., Newton V.E., Read A.P. (1994) Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. Nat Genet 8:251–255PubMedGoogle Scholar
  142. Thierfelder L., Watkins H., MacRae C. et al. (1994) Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophie cardiomyopathy: a disease of the sarcomere. Cell 77:701–712PubMedGoogle Scholar
  143. Torres M., Giraldez F. (1998) The development of the vertebrate inner ear. Mech Dev 71:5–21PubMedGoogle Scholar
  144. Tsuiki T., Murai S. (1971) Familial incidence of streptomycin hearing loss and hereditary weakness of the cochlea. Audiology 10:315–322PubMedGoogle Scholar
  145. Vahava O., Morell R., Lynch E.O. Waardenburg syndrome type 2 (1998) Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science 279:1950–1954PubMedGoogle Scholar
  146. Van Camp G., Coucke P., Balemans W. et al. (1995) Localization of a gene for non-syndromic hearing loss (OFNA5) to chromosome 7p15. Hum Mol Genet 4:2159–2163PubMedGoogle Scholar
  147. Van Camp G., Coucke P.J., Kunst H. et al. (1997) Linkage analysis of progressive hearing loss in five extended families maps the OFNA2 gene to a 1.25-Mb region on chromosome 1p. Genomics 41:70–74PubMedGoogle Scholar
  148. Van den Ouweland J.M., Lernkes H.H., Ruitenbeek W. et al. (1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type 11 diabetes mellitus and deafness. Nat Genet 1:368–371PubMedGoogle Scholar
  149. Van Laer L., Huizing E.H., Verstreken M. et al. (1998) Nonsyndromic hearing impairment is associated with a mutation in OFNA5. Nat Genet 20:194–197PubMedGoogle Scholar
  150. Verhoeven K., Van Camp G., Govaerts P.J. et al. (1997) A gene for autosomal dominant nonsyndromic hearing loss (OFNAI2) maps to chromosome 11q22-24. Am J Hum Genet 60:1168–1173PubMedGoogle Scholar
  151. Verhoeven K., Van Laer L., Kirschhofer K. et al. (1998) Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nat Genet 19:60–62PubMedGoogle Scholar
  152. Vetter O.E., Mann J.R., Wangemann P. et al. (1996) Inner ear defects induced by null mutation of the isk gene. Neuron 17:1251–1264PubMedGoogle Scholar
  153. Vincent G.M. (1998) The molecular genetics of the long QT syndrome: genes causing fainting and sudden death. Annu Rev Med 49:263–274PubMedGoogle Scholar
  154. Wallace O.C. (1993) Mitochondrial diseases: genotype versus phenotype. Trends Genet 9:128–133PubMedGoogle Scholar
  155. Wallace D.C. (1995) Mitochondrial DNA variation in human evolution, degenerative disease, and aging. Am J Hum Genet 57:201–223PubMedGoogle Scholar
  156. Wallis C., Ballo R., Wallis G., Beighton P., Goldblatt J. (1988) X-linked mixed deafness with stapes fixation in a Mauritian kindred: linkage to Xq probe pOP34. Genomics 3:299–301PubMedGoogle Scholar
  157. Wang Q., Curran M.E., Splawski I. et al. (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 12:17–23PubMedGoogle Scholar
  158. Wang A., Liang Y., Fridell R.A. et al. (1998) Association of unconventional myosin MY015 mutations with human nonsyndromic deafness DFNB3. Science 280:1447–1451PubMedGoogle Scholar
  159. Wangemann P. (1997) Potassium ion secretion and generation of the endocochlear potential in the stria vascularis. HNO 45:205–209PubMedGoogle Scholar
  160. Wangemann P., Liu J., Marcus O.C. (1995) Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro. Hear Res 84:19–29PubMedGoogle Scholar
  161. Wasserman S. (1998) FH proteins as cytoskeletal organizers. Trends Cell Biol 8:111–115PubMedGoogle Scholar
  162. Watanabe N., Madaule P., Reid T. et al. (1997) pl40mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 16:3044–3056PubMedGoogle Scholar
  163. Watkins H., Conner O., Thierfelder L. et al. (1995) Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet 11:434–437PubMedGoogle Scholar
  164. Weil D., Blanchard S., Kaplan J. et al. (1995) Defective myosin VIIA gene responsible for Usher syndrome type IB. Nature 374:60–61PubMedGoogle Scholar
  165. Weil D., Kussel P., Blanchard S. et al. (1997) The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet 16:191–193PubMedGoogle Scholar
  166. White T.W., Deans M.R., Kelsell O.P., Paul O.L. (1998) Connexin mutations in deafness. Nature 394:630–631PubMedGoogle Scholar
  167. Wollnik B., Guicheney P. (1994) Clinical and genetical aspects of the long QT syndrome. Herz 19:126–132PubMedGoogle Scholar
  168. Wollnik B., Schroeder B.C., Kubisch C., Esperer H.O., Wieacker P., Jentsch T.J. (1997) Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias. Hum Mol Genet 6:1943–1949PubMedGoogle Scholar
  169. Xia J.H., Liu C.Y., Tang B.S. et al. (1998) Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat Genet 20:370–373PubMedGoogle Scholar
  170. Zelante L., Gasparini P., Estivill X. et al. (1997) Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet 6:1605–1609PubMedGoogle Scholar
  171. Zeviani M., Muntoni F., Savarese N. et al. (1993) A MERRF/ MELAS overlap syndrome associated with a new point mutation in the mitochondrial ONA tRNA(Lys) gene. Eur J Hum Genet 1:80–87PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Christian Kubisch
  • Hanno Bolz
  • Andreas Gal

There are no affiliations available

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