REVIEW PAPER
NOVEL TRENDS IN THE MOLECULAR GENETICS OF HEARING LOSS
 
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Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw/Kajetany, Poland
CORRESPONDING AUTHOR
Monika Oldak   

Monika Oldak, Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Mochnackiego Str. 10, 02-042 Warsaw, Mokra Str. 17, Kajetany, 05-830 Nadarzyn Poland, Tel.: +48-22-356-03-66; Fax: +48-22-356-03-67; e-mail: m.oldak@ifps.org.pl
Publication date: 2020-04-15
 
J Hear Sci 2015;5(3):9–15
 
KEYWORDS
ABSTRACT
Genetically determined hearing loss is a highly heterogeneous disorder, and to date the analysis of its causes has been conducted selectively, covering only individual genes. Breakthroughs associated with current technological advances have contributed to a rapid development in the molecular genetics of hearing loss. Here we review a number of novel and important achievements in the field: application of next-generation sequencing, novel genes, and trends in molecular therapies for hearing loss. Current achievements in the molecular genetics of hearing loss are discussed in the context of previously published results and data from our own studies.
 
REFERENCES (46)
1.
Friedman TB, Griffith AJ. Human nonsyndromic sensorineural deafness. Annu Rev Genomics Hum Genet, 2003; 4: 341–402.
 
2.
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.
 
3.
Clark MJ, Chen R, Lam HY, Karczewski KJ, Chen R, Euskirchen G et al. Performance comparison of exome DNA sequencing technologies. Nat Biotechnol, 2011; 29(10): 908–14.
 
4.
Zhang J, Chiodini R, Badr A, Zhang G. The impact of nextgeneration sequencing on genomics. J Genet Genomics, 2011; 38(3): 95–109.
 
5.
Chen JM, Ferec C, Cooper DN. Revealing the human mutome. Clin Genet, 2010; 78(4): 310–20.
 
6.
Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature, 2009; 461(7261): 272–6.
 
7.
Brownstein Z, Friedman LM, Shahin H, Oron-Karni V, Kol N, Abu Rayyan A et al. Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in Middle Eastern families. Genome Biol, 2011; 12(9): R89.
 
8.
Martins FTA, Brownstein Z, Birkan M et al. Identification of deafness genes in Israeli Jewish and Brazilian families using Next Generation Sequencing platforms. Eur J Hum 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
9.
Danial-Farran N, Brownstein Z, Abu-Rayyan A et al. Identification of novel genes and mutations associated with hearing loss in the Middle Eastern Arab population by next generation sequencing. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
10.
Roux AF, Faugere V, Moclyn M et al. Prevalence of non-syndromic hearing loss genes in a cohort of French patients. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
11.
Boardman S, Mavrogiannis LA, Crinnion L, Watson CM, Charlton RS. Gene panel testing in non-syndromic hearing loss: validation on a British Asian cohort. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
12.
Song LJ, Yi YT. Panel base on next-generation sequencing for mutation detection in hearing impairment. Eur J Hum. 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
13.
Pollak A, Lechowicz U, Podgorska A et al. Genetically related hearing loss: results of exome sequencing in Polish patients. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
14.
Lechowicz U, Pollak A, Podgorska A et al. Profile of TMPRSS3 mutation among Polish patients with nonsyndromic hearing impairment. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
15.
Battelino S, Klancar G, Kovac J, Battelino T, Trebusak Podkrajsek K. TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss. Eur Arch Otorhinolaryngol, 2015 [Epub ahead of print].
 
16.
Abdelfatah N, Mostafa A, Stanton SG, et al. An in-frame deletion in FOXL1 identifies the first gene causing autosomal dominant otosclerosis. Eur J Hum. 2015;23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
17.
Declau F, Van Spaendonck M, Timmermans JP, Michaels L, Liang J, Qiu JP et al. Prevalence of otosclerosis in an unselected series of temporal bones. Otol Neurotol, 2001; 22(5): 596–602.
 
18.
Schrauwen I, Van Camp G. The etiology of otosclerosis: a combination of genes and environment. Laryngoscope, 2010; 120(6): 1195–202.
 
19.
Stanton S, Lucas M, Griffin A et al. The hearing phenotype associated with an in-frame deletion in FOXL1 causing autosomal dominant otosclerosis. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, Glasgow, U.K.).
 
20.
Priyadarshi S, Ray CS, Panda KC, Desai A, Nayak SR, Biswal NC et al. Genetic association and gene expression profiles of TGFB1 and the contribution of TGFB1 to otosclerosis susceptibility. J Bone Miner Res, 2013; 28(12): 2490–7.
 
21.
Girotto G, Scheffer DI, Morgan A et al. NGS revealed PSIP1/LEDGF as a new gene causing sensorineural progressive hearing loss and variable eye phenotypes. Eur J Hum, 2015; 23, Suppl. 1 (European Human Genetics Conference 2015; June 6–9, 2015 Glasgow, U.K.).
 
22.
Pradeepa MM, Sutherland HG, Ule J, Grimes GR, Bickmore WA. Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS Genet, 2012; 8(5): e1002717.
 
23.
Raz-Prag D, Zeng Y, Sieving PA, Bush RA. Photoreceptor protection by adeno-associated virus-mediated LEDGF expression in the RCS rat model of retinal degeneration: probing the mechanism. Invest Ophthalmol Vis Sci, 2009; 50(8): 3897–906.
 
24.
Ratbi I, Falkenberg KD, Sommen M et al. Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6. Am J Hum Genet, 2015 [Epub ahead of print].
 
25.
Lima LH, Barbazetto IA, Chen R, Yannuzzi LA, Tsang SH, Spaide RF. Macular dystrophy in Heimler syndrome. Ophthalmic Genet, 2011; 32(2): 97–100.
 
26.
Heimler A, Fox JE, Hershey JE, Crespi P. Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs. Am J Med Genet, 1991; 39(2): 192–5.
 
27.
Santos-Cortez RL, Lee K, Giese AP, Ansar M, Amin-Ud-Din M, Rehn K et al. Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish. Hum Mol Genet, 2014; 23(12): 3289–98.
 
28.
Girotto G, Abdulhadi K, Buniello A, Vozzi D, Licastro D, d’Eustacchio A et al. Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. PLoS One, 2013; 8(12): e80323.
 
29.
Diaz-Horta O, Subasioglu-Uzak A, Grati M, DeSmidt A, Foster J II, Cao L et al. FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing. Proc Natl Acad Sci USA, 2014; 111(27): 9864–8.
 
30.
Azaiez H, Decker AR, Booth KT, Simpson AC, Shearer AE, Huygen PL et al. HOMER2, a stereociliary scaffolding protein, is essential for normal hearing in humans and mice. PLoS Genet, 2015; 11(3): e1005137.
 
31.
Gao J, Wang Q, Dong C, Chen S, Qi Y, Liu Y. Whole exome sequencing identified MCM2 as a novel causative gene for autosomal dominant nonsyndromic deafness in a Chinese family. PLoS One, 2015; 10(7): e0133522.
 
32.
Mujtaba G, Schultz JM, Imtiaz A, Morell RJ, Friedman TB, Naz S. A mutation of MET, encoding hepatocyte growth factor receptor, is associated with human DFNB97 hearing loss. J Med Genet, 2015; 52(8): 548–52.
 
33.
Simon M, Richard EM, Wang X, Shahzad M, Huang VH, Qaiser TA et al. Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome. PLoS Genet, 2015; 11(3): e1005097.
 
34.
Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A et al. Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci USA, 2013; 110(6): 2228–33.
 
35.
Azaiez H, Booth KT, Bu F, Huygen P, Shibata SB, Shearer AE et al. TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss. Hum Mutat, 2014; 35(7): 819–23.
 
36.
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.
 
37.
Bedoyan JK, Schaibley VM, Peng W, Bai Y, Mondal K, Shetty AC et al. Disruption of RAB40AL function leads to MartinProbst syndrome, a rare X-linked multisystem neurodevelopmental human disorder. J Med Genet, 2012; 49(5): 332–40.
 
38.
Ołdak M, Ruszkowska E, Pollak A, Sobczyk-Kopcioł A, Kowalewski C, Piwońska A et al. A note of caution on the diagnosis of Martin-Probst syndrome by the detection of the p.D59G mutation in the RAB40AL gene. Eur J Pediatr, 2015; 174(5): 693–6.
 
39.
Ołdak M, Ścieżyńska A, Młynarski W, Borowiec M, Ruszkowska E, Szulborski K et al. Evidence against RAB40AL being the locus for Martin-Probst X-linked deafness – intellectual disability syndrome. Hum Mutat, 2014; 35(10): 1171–4.
 
40.
Donaudy F, Ferrara A, Esposito L, Hertzano R, Ben-David O, Bell RE et al. Multiple mutations of MYO1A, a cochlear-expressed gene, in sensorineural hearing loss. Am J Hum Genet, 2003; 72(6): 1571–7.
 
41.
Eisenberger T, Di Donato N, Baig SM, Neuhaus C, Beyer A, Decker E et al. Targeted and genomewide NGS data disqualify mutations in MYO1A, the “DFNA48 gene”, as a cause of deafness. Hum Mutat, 2014; 35(5): 565–70.
 
42.
Rivera T, Sanz L, Camarero G, Varela-Nieto I. Drug delivery to the inner ear: strategies and their therapeutic implications for sensorineural hearing loss. Curr Drug Deliv, 2012; 9(3): 231–42.
 
43.
Park YH, Wilson KF, Ueda Y, Tung Wong H, Beyer LA, Swiderski DL et al. Conditioning the cochlea to facilitate survival and integration of exogenous cells into the auditory epithelium. Mol Ther, 2014; 22(4): 873–80.
 
44.
Crispino G, Di Pasquale G, Scimemi P, Rodriguez L, Galindo Ramirez F, De Siati RD et al. BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice. PLoS One, 2011; 6(8): e23279.
 
45.
Yu Q, Wang Y, Chang Q, Wang J, Gong S, Li H, Lin X. Virally expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice. Gene Ther, 2014; 21(1): 71–80.
 
46.
Fukui H, Raphael Y. Gene therapy for the inner ear. Hear Res, 2013; 297: 99–105.