Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 7/2012

01-07-2012 | Review Article

Genetics of hearing loss: where are we standing now?

Authors: Hossein Mahboubi, Sami Dwabe, Matthew Fradkin, Virginia Kimonis, Hamid R. Djalilian

Published in: European Archives of Oto-Rhino-Laryngology | Issue 7/2012

Login to get access

Abstract

Hearing loss (HL) is the most common sensory impairment and is caused by a broad range of inherited to environmental causes. Inherited HL consists 50–60% of all HL cases. The inherited form of HL is further classified to different categories. More than 300 syndromes and 40 genes have been identified to result in different levels of HL. Although several diagnostic or screening tests have been developed, yet there are controversies around their use.
Literature
2.
go back to reference Wilde WR (1853) Practical observations on aural surgery and the nature and treatment of diseases of the ear. Churchill Livingstone, London Wilde WR (1853) Practical observations on aural surgery and the nature and treatment of diseases of the ear. Churchill Livingstone, London
3.
go back to reference Politzer A (1882) Lehrbruch der Ohrenheilkunde, vol 2. Enke, Stuttgart Politzer A (1882) Lehrbruch der Ohrenheilkunde, vol 2. Enke, Stuttgart
4.
go back to reference Marres HA (1998) Congenital abnormalities of the inner ear. In: Ludman H, Wright T (eds) Diseases of the ear. Arnold & Oxford University Press, Bath, pp 288–296 Marres HA (1998) Congenital abnormalities of the inner ear. In: Ludman H, Wright T (eds) Diseases of the ear. Arnold & Oxford University Press, Bath, pp 288–296
5.
go back to reference Toriello HV, Reardon W, Gorlin RJ (2004) Hereditary hearing loss and its syndromes. Oxford University Press, Oxford Toriello HV, Reardon W, Gorlin RJ (2004) Hereditary hearing loss and its syndromes. Oxford University Press, Oxford
6.
go back to reference Ouyang XM, Yan D, Yuan HJ, Pu D, Du LL, Han DY, Liu XZ (2009) The genetic bases for non-syndromic hearing loss among Chinese. J Hum Genet 54:131–140PubMedCrossRef Ouyang XM, Yan D, Yuan HJ, Pu D, Du LL, Han DY, Liu XZ (2009) The genetic bases for non-syndromic hearing loss among Chinese. J Hum Genet 54:131–140PubMedCrossRef
7.
go back to reference Kochhar A, Hildebrand MS, Smith RJ (2007) Clinical aspects of hereditary hearing loss. Genet Med 9:393–408PubMedCrossRef Kochhar A, Hildebrand MS, Smith RJ (2007) Clinical aspects of hereditary hearing loss. Genet Med 9:393–408PubMedCrossRef
9.
go back to reference Morton CC, Nance WE (2006) Newborn hearing screening—a silent revolution. N Engl J Med 354:2151–2164PubMedCrossRef Morton CC, Nance WE (2006) Newborn hearing screening—a silent revolution. N Engl J Med 354:2151–2164PubMedCrossRef
10.
go back to reference Mason JA, Herrmann KR (1998) Universal infant hearing screening by automated auditory brainstem response measurement. Pediatrics 101:221–228PubMedCrossRef Mason JA, Herrmann KR (1998) Universal infant hearing screening by automated auditory brainstem response measurement. Pediatrics 101:221–228PubMedCrossRef
11.
go back to reference Grundfast KM, Siparsky N, Chuong D (2000) Genetics and molecular biology of deafness. Update. Otolaryngol Clin North Am 33:1367–1394PubMedCrossRef Grundfast KM, Siparsky N, Chuong D (2000) Genetics and molecular biology of deafness. Update. Otolaryngol Clin North Am 33:1367–1394PubMedCrossRef
12.
15.
go back to reference Baldwin CT, Hoth CF, Amos JA, da Silva EO, Milunsky A (1992) An exonic mutation in the HuP2 paired domain gene causes Waardenburg’s syndrome. Nature 355:637–638PubMedCrossRef Baldwin CT, Hoth CF, Amos JA, da Silva EO, Milunsky A (1992) An exonic mutation in the HuP2 paired domain gene causes Waardenburg’s syndrome. Nature 355:637–638PubMedCrossRef
16.
go back to reference DeStefano AL, Cupples LA, Arnos KS et al (1998) Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations. Hum Genet 102:499–506PubMedCrossRef DeStefano AL, Cupples LA, Arnos KS et al (1998) Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations. Hum Genet 102:499–506PubMedCrossRef
17.
go back to reference Heimler A, Lieber E (1986) Branchio-oto-renal syndrome: reduced penetrance and variable expressivity in four generations of a large kindred. Am J Med Genet 25:15–27PubMedCrossRef Heimler A, Lieber E (1986) Branchio-oto-renal syndrome: reduced penetrance and variable expressivity in four generations of a large kindred. Am J Med Genet 25:15–27PubMedCrossRef
18.
go back to reference Ruf RG, Xu PX, Silvius D, Otto EA et al (2004) SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci USA 101:8090–8095PubMedCrossRef Ruf RG, Xu PX, Silvius D, Otto EA et al (2004) SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci USA 101:8090–8095PubMedCrossRef
19.
go back to reference Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M et al (1997) Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 17:411–422PubMedCrossRef Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M et al (1997) Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 17:411–422PubMedCrossRef
20.
21.
go back to reference Phelps PD, Coffey RA, Trembath RC, Luxon LM et al (1998) Radiological malformations of the ear in Pendred syndrome. Clin Radiol 53:268–273PubMedCrossRef Phelps PD, Coffey RA, Trembath RC, Luxon LM et al (1998) Radiological malformations of the ear in Pendred syndrome. Clin Radiol 53:268–273PubMedCrossRef
22.
go back to reference Kimberling WJ, Möller CG, Davenport SL, Lund G, Grissom TJ, Priluck I et al (1989) Usher syndrome: clinical findings and gene localization studies. Laryngoscope 99:66–72PubMedCrossRef Kimberling WJ, Möller CG, Davenport SL, Lund G, Grissom TJ, Priluck I et al (1989) Usher syndrome: clinical findings and gene localization studies. Laryngoscope 99:66–72PubMedCrossRef
23.
go back to reference Rosenberg T, Haim M, Hauch AM, Parving A (1997) The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations. Clin Genet 51:314–321PubMedCrossRef Rosenberg T, Haim M, Hauch AM, Parving A (1997) The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations. Clin Genet 51:314–321PubMedCrossRef
25.
go back to reference Govan JA (1983) Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes? Br J Ophthalmol 67:493–503PubMedCrossRef Govan JA (1983) Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes? Br J Ophthalmol 67:493–503PubMedCrossRef
26.
go back to reference Hutchin TP, Cortopassi GA (2000) Mitochondrial defects and hearing loss. Cell Mol Life Sci 57:1927–1937PubMedCrossRef Hutchin TP, Cortopassi GA (2000) Mitochondrial defects and hearing loss. Cell Mol Life Sci 57:1927–1937PubMedCrossRef
27.
go back to reference Jacobs HT, Hutchin TP, Kappi T et al (2005) Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment. Eur J Hum Genet 13:26–33PubMedCrossRef Jacobs HT, Hutchin TP, Kappi T et al (2005) Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment. Eur J Hum Genet 13:26–33PubMedCrossRef
28.
go back to reference Hilgert N, Smith RJ, Van Camp G (2009) Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 681:189–196PubMedCrossRef Hilgert N, Smith RJ, Van Camp G (2009) Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 681:189–196PubMedCrossRef
29.
go back to reference Van Laer L, McGuirt WT, Yang T, Smith RJH, Van Camp G (1999) Autosomal dominant nonsyndromic hearing impairment. Am J Med Genet 89:167–174PubMedCrossRef Van Laer L, McGuirt WT, Yang T, Smith RJH, Van Camp G (1999) Autosomal dominant nonsyndromic hearing impairment. Am J Med Genet 89:167–174PubMedCrossRef
30.
go back to reference Finsterer J, Fellinger J (2005) Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing. Int J Pediatr Otorhinolaryngol 69:621–647PubMedCrossRef Finsterer J, Fellinger J (2005) Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing. Int J Pediatr Otorhinolaryngol 69:621–647PubMedCrossRef
31.
go back to reference Hofmann S, Philbrook C, Gerbitz KD, Bauer MF (2003) Wolfram syndrome: structural and functional analyses of mutant and wild-type Wolframin, the WFS1 gene product. Hum Mol Genet 12:2003–2012PubMedCrossRef Hofmann S, Philbrook C, Gerbitz KD, Bauer MF (2003) Wolfram syndrome: structural and functional analyses of mutant and wild-type Wolframin, the WFS1 gene product. Hum Mol Genet 12:2003–2012PubMedCrossRef
32.
go back to reference Topsakal V, Pennings RJ, te Brinke H, Hamel B, Huygen PL, Kremer H, Cremers CW (2005) Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S). Otol Neurotol 26:52–58PubMedCrossRef Topsakal V, Pennings RJ, te Brinke H, Hamel B, Huygen PL, Kremer H, Cremers CW (2005) Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S). Otol Neurotol 26:52–58PubMedCrossRef
33.
go back to reference Van Camp G, Coucke PJ, Akita J, Fransen E, Abe S, De Leenheer EM, Huygen PL, Cremers CW, Usami S (2002) A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment. Hum Mutat 20:15–19PubMedCrossRef Van Camp G, Coucke PJ, Akita J, Fransen E, Abe S, De Leenheer EM, Huygen PL, Cremers CW, Usami S (2002) A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment. Hum Mutat 20:15–19PubMedCrossRef
34.
go back to reference Pfister M, Thiele H, Van Camp G, Fransen E, Apaydin F, Aydin O et al (2004) A genotype–phenotype correlation with gender-effect for hearing impairment caused by TECTA mutations. Cell Physiol Biochem 14:369–376PubMedCrossRef Pfister M, Thiele H, Van Camp G, Fransen E, Apaydin F, Aydin O et al (2004) A genotype–phenotype correlation with gender-effect for hearing impairment caused by TECTA mutations. Cell Physiol Biochem 14:369–376PubMedCrossRef
35.
go back to reference Denoyelle F, Marlin S, Weil D, Moatti L, Chauvin P, Garabédian EN, Petit C (1999) Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet 353:1298–1303PubMedCrossRef Denoyelle F, Marlin S, Weil D, Moatti L, Chauvin P, Garabédian EN, Petit C (1999) Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet 353:1298–1303PubMedCrossRef
36.
go back to reference Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE et al (2001) Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype–phenotype correlations. Hum Mutat 17:403–411PubMedCrossRef Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE et al (2001) Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype–phenotype correlations. Hum Mutat 17:403–411PubMedCrossRef
37.
go back to reference Guan MX (2004) Molecular pathogenetic mechanism of maternally inherited deafness. Ann N Y Acad Sci 1011:259–271PubMedCrossRef Guan MX (2004) Molecular pathogenetic mechanism of maternally inherited deafness. Ann N Y Acad Sci 1011:259–271PubMedCrossRef
38.
39.
go back to reference Xing G, Chen Z, Cao X (2007) Mitochondrial rRNA and tRNA and hearing function. Cell Res 17:227–239PubMed Xing G, Chen Z, Cao X (2007) Mitochondrial rRNA and tRNA and hearing function. Cell Res 17:227–239PubMed
40.
go back to reference Fischel-Ghodsian N, Prezant TR, Chaltraw WE, Wendt KA, Nelson RA, Arnos KS, Falk RE (1997) Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity. Am J Otolaryngol 18:173–178PubMedCrossRef Fischel-Ghodsian N, Prezant TR, Chaltraw WE, Wendt KA, Nelson RA, Arnos KS, Falk RE (1997) Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity. Am J Otolaryngol 18:173–178PubMedCrossRef
41.
go back to reference Hilgert N, Smith RJ, Van Camp G (2009) Function and expression pattern of nonsyndromic deafness genes. Curr Mol Med 9:546–564PubMedCrossRef Hilgert N, Smith RJ, Van Camp G (2009) Function and expression pattern of nonsyndromic deafness genes. Curr Mol Med 9:546–564PubMedCrossRef
42.
go back to reference Stockley TL, Mendoza-Londono R, Propst EJ, Sodhi S, Dupuis L, Papsin BC (2009) A recurrent EYA1 mutation causing alternative RNA splicing in branchio-oto-renal syndrome: implications for molecular diagnostics and disease mechanism. Am J Med Genet A 149A:322–327PubMedCrossRef Stockley TL, Mendoza-Londono R, Propst EJ, Sodhi S, Dupuis L, Papsin BC (2009) A recurrent EYA1 mutation causing alternative RNA splicing in branchio-oto-renal syndrome: implications for molecular diagnostics and disease mechanism. Am J Med Genet A 149A:322–327PubMedCrossRef
43.
go back to reference Bhuiyan ZA, Momenah TS, Amin AS et al (2008) An intronic mutation leading to incomplete skipping of exon-2 in KCNQ1 rescues hearing in Jervell and Lange-Nielsen syndrome. Prog Biophys Mol Biol 98:319–327PubMedCrossRef Bhuiyan ZA, Momenah TS, Amin AS et al (2008) An intronic mutation leading to incomplete skipping of exon-2 in KCNQ1 rescues hearing in Jervell and Lange-Nielsen syndrome. Prog Biophys Mol Biol 98:319–327PubMedCrossRef
44.
go back to reference Esmaeili M, Bonyadi M, Nejadkazem M (2007) Common mutation analysis of GJB2 and GJB6 genes in affected families with autosomal recessive non-syndromic hearing loss from Iran: simultaneous detection of two common mutations (35delG/del(GJB6-D13S1830)) in the DFNB1-related deafness. Int J Pediatr Otorhinolaryngol 71:869–873PubMedCrossRef Esmaeili M, Bonyadi M, Nejadkazem M (2007) Common mutation analysis of GJB2 and GJB6 genes in affected families with autosomal recessive non-syndromic hearing loss from Iran: simultaneous detection of two common mutations (35delG/del(GJB6-D13S1830)) in the DFNB1-related deafness. Int J Pediatr Otorhinolaryngol 71:869–873PubMedCrossRef
45.
go back to reference Bu X, Shohat M, Jaber L, Rotter JI (1993) A form of sensorineural deafness is determined by a mitochondrial and an autosomal locus: evidence from pedigree segregation analysis. Genet Epidemiol 10:3–15PubMedCrossRef Bu X, Shohat M, Jaber L, Rotter JI (1993) A form of sensorineural deafness is determined by a mitochondrial and an autosomal locus: evidence from pedigree segregation analysis. Genet Epidemiol 10:3–15PubMedCrossRef
46.
go back to reference Kothiyal P, Cox S, Ebert J, Husami A, Kenna MA, Greinwald JH, Aronow BJ, Rehm HL (2010) High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays. BMC Biotechnol 10:10PubMedCrossRef Kothiyal P, Cox S, Ebert J, Husami A, Kenna MA, Greinwald JH, Aronow BJ, Rehm HL (2010) High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays. BMC Biotechnol 10:10PubMedCrossRef
47.
go back to reference Hildebrand MS, DeLuca AP, Taylor KR, Hoskinson DP, Hur IA, Tack D, McMordie SJ, Huygen PL, Casavant TL, Smith RJ (2009) A contemporary review of AudioGene audioprofiling: a machine-based candidate gene prediction tool for autosomal dominant nonsyndromic hearing loss. Laryngoscope 119:2211–2215PubMedCrossRef Hildebrand MS, DeLuca AP, Taylor KR, Hoskinson DP, Hur IA, Tack D, McMordie SJ, Huygen PL, Casavant TL, Smith RJ (2009) A contemporary review of AudioGene audioprofiling: a machine-based candidate gene prediction tool for autosomal dominant nonsyndromic hearing loss. Laryngoscope 119:2211–2215PubMedCrossRef
48.
go back to reference Rehm HL (2005) A genetic approach to the child with sensorineural hearing loss. Semin Perinatol 29:173–181PubMedCrossRef Rehm HL (2005) A genetic approach to the child with sensorineural hearing loss. Semin Perinatol 29:173–181PubMedCrossRef
49.
go back to reference Chan DK, Schrijver I, Chang KW (2011) Diagnostic yield in the workup of congenital sensorineural hearing loss is dependent on patient ethnicity. Otol Neurotol 32:81–87PubMedCrossRef Chan DK, Schrijver I, Chang KW (2011) Diagnostic yield in the workup of congenital sensorineural hearing loss is dependent on patient ethnicity. Otol Neurotol 32:81–87PubMedCrossRef
50.
go back to reference Matsunaga T (2009) Value of genetic testing in the otological approach for sensorineural hearing loss. Keio J Med 58:216–222PubMedCrossRef Matsunaga T (2009) Value of genetic testing in the otological approach for sensorineural hearing loss. Keio J Med 58:216–222PubMedCrossRef
51.
go back to reference Meyer NC, Nishimura CJ, McMordie S, Smith RJ (2007) Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree. Clin Genet 72:130–137PubMedCrossRef Meyer NC, Nishimura CJ, McMordie S, Smith RJ (2007) Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree. Clin Genet 72:130–137PubMedCrossRef
52.
go back to reference de Heer AM, Schraders M, Oostrik J, Hoefsloot L, Huygen PL, Cremers CW (2011) Audioprofile-directed successful mutation analysis in a DFNA2/KCNQ4 (p.Leu274His) family. Ann Otol Rhinol Laryngol 120:243–248PubMed de Heer AM, Schraders M, Oostrik J, Hoefsloot L, Huygen PL, Cremers CW (2011) Audioprofile-directed successful mutation analysis in a DFNA2/KCNQ4 (p.Leu274His) family. Ann Otol Rhinol Laryngol 120:243–248PubMed
53.
go back to reference Hildebrand MS, Newton SS, Gubbels SP, Sheffield AM, Kochhar A, de Silva MG, Dahl HH, Rose SD, Behlke MA, Smith RJ (2008) Advances in molecular and cellular therapies for hearing loss. Mol Ther 16:224–236PubMedCrossRef Hildebrand MS, Newton SS, Gubbels SP, Sheffield AM, Kochhar A, de Silva MG, Dahl HH, Rose SD, Behlke MA, Smith RJ (2008) Advances in molecular and cellular therapies for hearing loss. Mol Ther 16:224–236PubMedCrossRef
Metadata
Title
Genetics of hearing loss: where are we standing now?
Authors
Hossein Mahboubi
Sami Dwabe
Matthew Fradkin
Virginia Kimonis
Hamid R. Djalilian
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
European Archives of Oto-Rhino-Laryngology / Issue 7/2012
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-011-1910-6

Other articles of this Issue 7/2012

European Archives of Oto-Rhino-Laryngology 7/2012 Go to the issue