GENETICS OF HUMAN HEREDITARY HEARING IMPAIRMENT
AbstractHereditary hearing impairment is heterogeneous type of disorder which can be caused due to environmental as well as genetical factors. Two distinct types of hereditary hearing loss are syndromic or non-syndromic. Non-syndromic hearing loss is further categorized as autosomal recessive, autosomal dominant, X-linked and mitochondrial deafness. Autosomal recessive occurs more frequently as compared to autosomal dominant. Mutations in various genes are responsible for hereditary hearing impairment. To date, about 99 autosomal recessives and 67 autosomal dominant genes for deafness have been discovered. Some of important genes include GJB2, JGB6, GJB3 which encodes gap junction proteins, MYO7A, MYO15A encodes myosine proteins, OTOF encodes otoferlin, and SLC26A4 encodes anion exchanger protein. Up till now, the mutation in GJB2 gene occurs more frequently in different population of the world and cause autosomal recessive hearing impairment. The purpose of this review article was to explore the mutation and function of those muted genes which encode different type of protein and responsible either for autosomal recessive or autosomal dominant hearing impairment.Keywords: Recessive deafness, Dominant deafness, Mutation, Encoded proteins, Genetics
Friedman TB, Griffith AJ. Human nonsyndromic Sensorineural Deafness. Annu Rev Genomics Hum Genet 2003;4(1):341–402.
Morton CC, Nance WE. Newborn hearing screening—a silent revolution. N Engl J Med 2006;354(20):2151–64.
Raviv D, Dror AA, Avraham KB. Hearing loss: a common disorder caused by many rare alleles. Ann N Y Acad Sci 2010;1214(1):168–79.
Petit C, Levilliers J, Hardelin JP. Molecular genetics of hearing loss. Annu Rev Genet 2001;35(1):589–645.
Smith RJ, Bale JF Jr, White KR. Sensorineural hearing loss in children. Lancet 2005;365(9462):879–90.
Mustapha M, Salem N, Delague V, Chouery E, Ghassibeh M, Rai M, et al. Autosomal recessive non-syndromic hearing loss in the Lebanese population: prevalence of the 30delG mutation and report of two novel mutations in the connexin 26 (GJB2) gene. J Med Genet 2001;38(10):E36.
Van Camp G, Willems PJ, Smith RJ. Nonsyndromic hearing impairment: unparalleled heterogeneity. Am J Hum Genet 1997;60(4):758–64.
Smith RJ, Shearer AE, Hildebrand MS, Van Camp G. Deafness and Hereditary Hearing Loss Overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al. editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2016 May 31]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1434/
Hussain R, Bittles AH. The prevalence and demographic characteristics of consanguineous marriages in Pakistan. J Biosoc Sci 1998;30(2):261–75.
Elahi MM, Elahi F, Elahi A, Elahi SB. Paediatric hearing loss in rural Pakistan. J Otolaryngol 1998;27(6):348–53.
Brown KA, Janjua AH, Karbani G, Parry G, Noble A, Crockford G, et al. Linkage studies of non-syndromic recessive deafness (NSRD) in a family originating from the Mirpur region of Pakistan maps DFNB1 centromeric to D13S175. Hum Mol Genet 1996;5(1):169–73.
Zakzouk S. Consanguinity and hearing impairment in developing countries: a custom to be discouraged. J Laryngol Otol 2002;116(10):811–6.
Li J, Zhao X, Xin Q, Shan S, Jiang B, Jin Y, et al. Whole‐Exome Sequencing Identifies a Variant in TMEM132E Causing Autosomal‐Recessive Nonsyndromic Hearing Loss DFNB99. Hum Mutat 2015;36(1):98–105.
Thoenes M, Zimmermann U, Ebermann I, Ptok M, Lewis MA, Thiele H, et al. OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67). Orphanet J Rare Dis 2015;10:15.
Rost S, Bach E, Neuner C, Nanda I, Dysek S, Bittner RE, et al. Novel form of X-linked nonsyndromic hearing loss with cochlear malformation caused by a mutation in the type IV collagen gene COL4A6. Eur J Hum Genet 2014;22(2):208–15.
Hilgert N, Smith RJ, Van Camp G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 2009;681(2-3):189–96.
de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, De Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991;174(5):1209–20.
Harris AL. Emerging issues of connexin channels: biophysics fills the gap. Q Rev Biophys 2001;34(3):325–472.
Kumar NM, Gilula NB. The gap junction communication channel. Cell 1996;84(3):381–8.
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(6628):80–3.
Zelante L, Gasparini P, Estivill X, Melchionda S, D'Agruma L, Govea N, et al. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet 1997;6(9):1605–9.
Denoyelle F, Lina-Granade G, Plauchu H, Bruzzone R, Chaïb H, Lévi-Acobas F, et al. Connexin 26 gene linked to a dominant deafness. Nature 1998;393(6683):319–20.
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(9100):394–8.
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(4):792–9.
Wang A, Liang Y, Fridell RA, Probst FJ, Wilcox ER, Touchman JW, et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science 1998;280(5368):1447–51.
Kenneson A, Van Naarden Braun K, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review. Genet Med 2002;4(4):258–74.
Rabionet R, Zelante L, López-Bigas N, D'Agruma L, Melchionda S, Restagno G, et al. Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. Hum Genet 2000;106(1):40–4.
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(12):2173–7.
Fuse Y, Doi K, Hasegawa T, Sugii A, Hibino H, Kubo T. Three novel connexin26 gene mutations in autosomal recessive nonsyndromic deafness. Neuroreport 1999;10(9):1853–7.
Xia JH, Liu CY, Tang BS, Pan Q, Huang L, Dai HP, et al. Mutations in the gene encoding gap junction protein β-3 associated with autosomal dominant hearing impairment. Nat Genet 1998;20(4):370–3.
Wenzel K, Manthey D, Willecke K, Grzeschik KH, Traub O. Human gap junction protein connexin31: molecular cloning and expression analysis. Biochem Biophys Res Commun 1998;248(3):910–5.
Macari F, Landau M, Cousin P, Mevorah B, Brenner S, Panizzon R, et al. Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis. Am J Hum Genet 2000;67(5):1296–301.
Xia JH, Liu CY, Tang BS, Pan Q, Huang L, Dai HP, et al. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat Genet 1998;20(4):370–3.
Lerer I, Sagi M, Ben‐Neriah Z, Wang T, Levi H, Abeliovich D. A deletion mutation in GJB6 cooperating with a GJB2 mutation in trans in non‐syndromic deafness: a novel founder mutation in Ashkenazi Jews. Hum Mutat 2001;18(5):460.
Kikuchi T, Kimura RS, Paul DL, Takasaka T, Adams JC. Gap junction systems in the mammalian cochlea. Brain Res Rev 2000;32(1):163–6.
Kelley PM, Abe S, Askew JW, Smith SD, Usami SI, Kimberling WJ. Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12. Genomics 1999;62(2):172–6.
Stenson PD, Mort M, Ball EV, Shaw K, Phillips AD, Cooper DN. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet 2014;133(1):1–9.
Yamazaki Y, Okawa K, Yano T, Tsukita S, Tsukita S. Optimized Proteomic Analysis on Gels of Cell− Cell Adhering Junctional Membrane Proteins. Biochemistry 2008;47(19):5378–86.
Kniesel U, Wolburg H. Tight junctions of the blood–brain barrier. Cell Mol Neurobiol 2000;20(1):57–76.
Wilcox ER, Burton QL, Naz S, Riazuddin S, Smith TN, Ploplis B, et al. Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 2001;104(1):165–72.
Lee K, Ansar M, Andrade PB, Khan B, Santos‐Cortez RL, Ahmad W, et al. Novel CLDN14 mutations in Pakistani families with autosomal recessive non‐syndromic hearing loss. Am J Med Genet A 2012;158A(2):315–21.
Mooseker MS, Cheney RE. Unconventional myosins. Annu Rev Cell Dev Biol 1995;11(1):633–75.
Krendel M, Mooseker MS. Myosins: tails (and heads) of functional diversity. Physiology (Bethesda) 2005;20(4):239–51.
Friedman TB, Sellers JR, Avraham KB. Unconventional myosins and the genetics of hearing loss. Am J Med Genet 1999;89(3):147–57.
Guilford P, Arab SB, Blanchard S, Levilliers J, Weissenbach J, Belkahia A, et al. A non–syndromic form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q. Nat Genet 1994;6(1):24–8.
Liu XZ, Walsh J, Mburu P, Kendrick-Jones J, Cope MJ, Steel KP, et al. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet 1997;16(2):188–90.
Adato A, Weil D, Kalinski H, Pel-Or Y, Ayadi H, Petit C, et al. Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis in Usher 1B families from diverse origins. Am J Hum Genet 1997;61(4):813–21.
Friedman TB, Liang Y, Weber JL, Hinnant JT, Barber TD, Winata S, et al. A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat Genet 1995;9(1):86–91.
Babanejad M, Fattahi Z, Bazazzadegan N, Nishimura C, Meyer N, Nikzat N, et al. A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. Am J Med Genet A 2012;158A(10):2485–92.
Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999;21(4):440–3.
Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, et al. Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex. Am J Physiol Renal Physiol 2001;280(2):F356–64.
Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE, et al. Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype–phenotype correlations. Hum Mutat 2001;17(5):403–11.
Pryor SP, Madeo AC, Reynolds JC, Sarlis NJ, Arnos KS, Nance WE, et al. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet 2005;42(2):159–65.
Marcotti W, Erven A, Johnson SL, Steel KP, Kros CJ. Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea. J Physiol 2006;574(Pt 3):677–98.
Nakanishi H, Kurima K, Kawashima Y, Griffith AJ. Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction. Auris Nasus Larynx 2014;41(5):399–408.
Ben said M, Hmani-Aifa M, Amar I, Baig SM, Mustapha M, Delmaghani S, et al. High frequency of the p. R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects. Genet Test Mol Biomark 2010;14(3):307–11.
Naz S, Giguere CM, Kohrman DC, Mitchem KL, Riazuddin S, Morell RJ, et al. Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus. Am J Hum Genet 2002;71(3):632–6.
Mitchem KL, Hibbard E, Beyer LA, Bosom K, Dootz GA, Dolan DF, et al. Mutation of the novel gene Tmie results in sensory cell defects in the inner ear of spinner, a mouse model of human hearing loss DFNB6. Hum Mol Genet 2002;11(16):1887–98.
Yang JJ, Su MC, Chien KH, Hsin CH, Li SY. Identification of novel variants in the TMIE gene of patients with nonsyndromic hearing loss. Int J Pediatr Otorhinolaryngol 2010;74(5):489–93.
Yasunaga SI, Petit C. Physical map of the region surrounding the OTOFERLIN locus on chromosome 2p22–p23. Genomics 2000;66(1):110–2.
Yasunaga SI, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, et al. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet 1999;21(4):363–9.
Chiu YH, Wu CC, Lu YC, Chen PJ, Lee WY, Liu AY, et al. Mutations in the OTOF gene in Taiwanese patients with auditory neuropathy. Audiol Neurotol 2010;15(6):364–74.
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.