Understanding the genetic basis of hearing loss is important because almost 50% of profound hearing loss are caused by genetic factors and more than 120 independent genes have been identified. In this review, after a brief explanation of some genetic terms (allele, heterozygosis, homozygosis, polymorphism, genotype and phenotype), classification of genetic hearing loss (syndromic versus nonsyndromic, and recessive dominant, X-linked and mitochondrial) was performed. Some of the most common syndromes (Usher, Pendred, Jervell and Lange-Nielsen, Waardenburg, branchio-oto-renal, Stickler, Treacher Collins and Alport syndromes, biotinidase deficiency and Norrie disease) causing genetic hearing loss were also explained briefly. The genes involved in hearing loss and genetic heterogeneity were presented.
© 2006 S. Karger AG, Basel
- Hereditary hearing loss
- Syndromic hearing loss
- Nonsyndromic hearing loss
- X-linked hearing loss
- Mitochondrial hearing loss
- Lalwani AK, Castelein CM: Cracking the auditory genetic code: Nonsyndromic hereditory hearing impairments. Am J Otol 1999;20:115–132.
- Tekin M, Arnos KS, Pandya A: Advances in hereditary deafness. Lancet 2001;358:1082–1090.
- Bayazit YA, Cable BB, Cataloluk O, Kara C, Chamberlin P, Smith RJ, Kanlikama M, Ozer E, Cakmak EA, Mumbuc S, Arslan A: GJB2 gene mutations causing familial hereditary deafness in Turkey. Int J Pediatr Otorhinolaryngol 2003;67:1331–1335.
- van Camp G, Smith JR: Hereditary hearing loss home-page. http://www.uia.ac.be/dnalab/hhh, 2003.
- Grundfast KM, Atwood JL, Chuong D: Genetics and molecular biology of deafness. Otolaryngol Clin North Am 1999;32:1067–1088.
- Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, et al: Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 1997;387:80–83.
- Denoyelle F, Marlin S, Weil D, Moatti L, Chauvin P, Garabedian EN, et al: Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: Implications for genetic counseling. Lancet 1999;353:1298–1303.
- Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, Fisher R, et al: Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N Eng J Med 1998;339:1500–1505.
- Abe S, Usami S, Shinkawa H, Kelley PM, Kimberling WJ: Prevalent connexin 26 gene (GJB2) mutations in Japanese. J Med Genet 2000;37:41–43.
- Zelante L, Gasparini P, Estivill X, Melchionda S, D’Agruma L, Govea N, et al: Connexin 26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet 1997;6:1605–1609.
- Kelley PM, Harris DJ, Comer BC, Askew JW, Fowler T, Smith SD, et al: Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss. Am J Hum Genet 1998;62:792–799.
- Carrasquillo MM, Zlotogora J, Barges S. Chakravarti, A: Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: Implications for genetic studies in isolated populations. Hum Mol Genet 1997;6:2163–2172.
- Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, et al: Prelingual deafness: High prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet 1997;6:2173–2177.
- Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D’Agruma L, et al: Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet 1998;351:394–398.
- Scott DA, Kraft ML, Stone EM, Sheffield VC, Smith RJ: Connexin mutations and hearing loss. Nature 1998;391:32.
- Topol EJ, Califf RM, Wilcox R, et al: Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa. N Engl J Med 1998;338:546–547.
- de Kok YJM, van der Maarel SM, Bitner-Glindzicz M, et al: Association between X-linked mixed deafness and mutation in the POU domain gene POU3F4. Science 1995;267:685–688.
- Smith RJ, Berlin CI, Hejtmancik JF, Keats BJ, Kimberling WJ, Lewis RA, et al: Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet 1994;50:32–38.
- Reardon W, Coffey R, Phelps PD, Luxon LM, Stephens D, Kendall-Taylor P, et al: Pendred syndrome – 100 years of underascertainment? QJM 1997;90:443–447.
- Li XC, Everett LA, Lalwani AK, Desmukh D, Friedman TB, Green ED, et al: A mutation in PDS causes non-syndromic recessive deafness. Nat Genet 1998;18:215–217.
- Splawski I, Timothy KW, Vincent GM, Atkinson DL, Keating MT: Molecular basis of the long-QT syndrome associated with deafness. N Engl J Med 1997;336:1562–1567.
- Nance WE: The genetics of deafness. Ment Retard Dev Disabil Res Rev 2003;9:109–119.
- Abdelhak S, Kalatzis V, Heilig R, et al: A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome gene and identifies a novel gene family. Nat Genet 1997;15:157–164.
- van Steensel MA, Buma P, de Waal Malefijt MC, van den Hoogen FH, Brunner HG: Oto-spondylo-megaepiphyseal dysplasia (OSMED): Clinical description of three patients homozygous for a missense mutation in the COL11A2 gene. Am J Med Genet 1997;70:315–323.
- Fischel-Ghodsian N, Prezant TR, Chaltraw WE, et al: Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity. Am J Otolaryngol 1997;18:173–178.
- Hardisty RE, Mburu P, Brown SD: ENU mutagenesis and search for deafness genesis. Br J Audiol 1999;33:279–283.
- Petit C: Genes responsible for human hereditary deafness: Symptoms of thousand. Nat Genet 1996;14:385–391.
- De Leenheer EMR, Kunst HPM, McGuirt WT, Prasad SD, Brown MR, Huygen PLM, Smith RJH, Cremers CWRJ: Autosomal dominant inherited hearing impairment caused by a missense mutation in COL11A2 (DFN13). Arch Otolaryngol 2001;127:13–17.
- Tamagawa Y, Ishikawa K, Ishikawa K, Ishida T, Kitamura K, Maniko S, Tsuru T, Ichimura K: Phenotype of DFNA11: A nonsyndromic hearing loss caused by a myosin VIIA mutation. Laryngoscope 2002;112:292–297.
- Smith RJH, Hone S: Genetic screening for deafness. Pediatr Clin North Am 2003;50:315–329.
- Chen AH, Stephan DA, Hassan T, Fukushima K, Nelissen CM, Chen AF, Jun AI, Ramesh A, Van Camp G, Smith RJH: MYO1F as a candidate gene for nonsyndromic deafness, DFNB15. Arch Otolaryngol Head Neck Surg 2001;172:921–925.
- Chen AH, Mueller RI, Prasad SD, Greinwald JH, Manaligod J, Muilenburg AC, Verhoeven K, Camp GV, Smith RJH: Presymptomtomatic diagnosis of nonsyndromix hearing loss by genotyping. Arch Otolaryngol Head Neck Surg 1998;124:20–24.
- Praetorius M, Baker K, Weich CM, Plinkert PK, Staecker H: Hearing preservation after inner ear gene therapy: The effect of vector and surgical approach. ORL J Otorhinolaryngol Relat Spec 2003;65:211–214.
- Kawamoto K, Oh SH, Kanzaki S, Brown N, Raphael Y: The functional and structural outcome of inner ear gene transfer via the vestibular and cochlear fluids in mice. Mol Ther 2001;4:575–585.
Yildirim A. Bayazit, MD
Department of Otolaryngology, Faculty of Medicine, Gazi University
Besevler, TR–Ankara (Turkey)
Tel. +90 312 202 6426, Fax +90 312 430 6648
Received: June 3, 2004
Accepted: September 9, 2004
Published online: January 20, 2006
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 6, Number of References : 34
ORL (Journal for Oto-Rhino-Laryngology and Ist Related Specialties)
Vol. 68, No. 2, Year 2006 (Cover Date: March 2006)
Journal Editor: O'Malley, B.W., Jr. (Philadelphia, Pa.)
ISSN: 0301–1569 (print), 1423–0275 (Online)
For additional information: http://www.karger.com/ORL
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