Identification of nonsense mutation in TMC1 gene inducing hearing loss by clinical exome sequencing

  • Maryam Alobathani Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Abdullah Al Mutery Molecular Genetics Research Laboratory, University of Sharjah, Sharjah, United Arab Emirates
  • Walaa Kamal Eddine Ahmad Mohamed Universitat Autónoma de Barcelona, Spain.
  • Abdelaziz Tlili Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.

Abstract

Hearing loss is one of the most common sensorineural disorders, affecting one in 1000 individuals that can be classified into syndromic and non-syndromic. TMC1 gene has been identified as a non-syndromic gene for both autosomal and recessive forms. In this study, we characterized a UAE consanguineous family with congenital profound non-syndromic hearing loss. By using clinical exome sequencing, Sanger sequencing and PCR-RFLP, we identified the p.Arg34X as the disease-associated variant. The screening of other families with deafness, revealed the presence of this nonsense mutation in one additional family and suggested that p.Arg34X is major contributor to DFNB7/11 form of deafness in UAE population. To the best of our knowledge, this is the first study associating TMC1 mutations to hearing loss in the GCC region. 

References

Belguith H, Tlili A, Dhouib H, Dhouib H, Rebeh I , Lahmar I,Charfeddine I, Driss N, Ghorbel A, Ayadi H ,Masmoudi S (2009) Mutation in gap and tight junctions in patients with non-syndromic hearing loss. Biochem Biophys Res Commun 385:1-5.

Ben Said M, Hmani-Aifa M, Amar I, Mahmood Baig S,Mustapha M, Delmaghani S, Tlili A, Ghorbel A, Ayadi H, Van Camp G, J.H. Smith R, Tekin M, and Masmoudi S (2010) High frequency of the p.R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects. Genet Test Mol Biomarkers 14:307-311.

Egilmez OK, Kalcioglu MT (2016) Genetics of Nonsyndromic Congenital Hearing Loss. Scientifica (Cairo). 2016: 7576064.

Hilgert N, Alasti F, Dieltjens N, Pawlik B, Wollnik B, Uyguner O, Delmaghani S, Weil D, Petit C, Danis E, Yang T, Pandelia E, B. Petersen M, Goossens D, Del Favero J, Hossein Sanati M, JH Smith R, and Van Camp G (2008) Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7/11. Clin Genet 74:223-232.

Kalay E, Karaguzel A, Caylan R , Heister A, Cremers FP, Cremers CW, Brunner HG, de Brouwer AP, Kremer H.(2005) Four novel TMC1 (DFNB7/DFNB11) mutations in Turkish patients with congenital autosomal recessive nonsyndromic hearing loss. Hum Mutat 26:591.

Kawashima Y, Kurima K, Pan B, Griffith AJ, Holt JR.(2015) Transmembrane channel-like (TMC) genes are required for auditory and vestibular mechanosensation. Pflugers Arch 467:85-94.

Keats BJ, Nouri N, Huang JM, Money M, Webster DB, Berlin CI. (1995) The deafness locus (dn) maps to mouse chromosome 19. Mamm Genome 6:8-10.

Kitajiri SI, McNamara R, Makishima T, Husnain T, Zafar AU, Kittles RA, Ahmed ZM, Friedman TB, Riazuddin S, Griffith AJ.(2007) Identities, frequencies and origins of TMC1 mutations causing DFNB7/B11 deafness in Pakistan. Clin Genet 72:546-550.

Kurima K, Peters LM, Yang Y, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo J, Makishima T, Ghosh M, Menon PS, Deshmukh D, Oddoux C, Ostrer H, Khan S, Riazuddin S, Deininger PL, Hampton LL, Sullivan SL, Battey JF Jr, Keats BJ, Wilcox ER, Friedman TB, Griffith AJ. (2002a) Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet 30:277-284.

Kurima K, Peters LM, Yang Y, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo J, Makishima T, Ghosh M, Menon PS, Deshmukh D, Oddoux C, Ostrer H, Khan S, Riazuddin S, Deininger PL, Hampton LL, Sullivan SL, Battey JF Jr, Keats BJ, Wilcox ER, Friedman TB, Griffith AJ. (2002b) Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet 30:277-284.

Lu Y, Yao J, Wei Q, Lu YYao JXu J, Xing G, Cao X (2018) Genetic analysis of CLDN14 in the Chinese population affected with non-syndromic hearing loss. Int J Pediatr Otorhinolaryngol 105:6-11.

Maeda R, Kindt KS, Mo W, Morgan CP, Erickson T, Zhao H, Clemens-Grisham R, Barr-Gillespie PG, Nicolson T. (2014) Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. Proc Natl Acad Sci U S A 111:12907-12912.

Pan B, Geleoc GS, Asai Y, Horwitz GC, Kurima K, Ishikawa K, Kawashima Y, Griffith AJ, Holt JR.(2013) TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. Neuron 79:504-515.

Pan B, Holt JR (2015) The molecules that mediate sensory transduction in the mammalian inner ear. Curr Opin Neurobiol 34:165-171.

Riazuddin S, Belyantseva IA, Giese AP, Lee K, Indzhykulian AA, Nandamuri SP, Yousaf R, Sinha GP, Lee S, Terrell D, Hegde RS, Ali RA, Anwar S, Andrade-Elizondo PB, Sirmaci A, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Ahmad W, Khan SN, Akram J, Tekin M, Riazuddin S, Cook T, Buschbeck EK, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZM. (2012) Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet 44:1265-1271.

Schrauwen I, Sommen M, Corneveaux JJ, Reiman RA, Hackett NJ, Claes C, Claes K, Bitner-Glindzicz M, Coucke P, Van Camp G, Huentelman MJ. (2013) A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing. Am J Med Genet A 161A:145-152.

Scott DA, Carmi R, Elbedour K, Yosefsberg S, Stone EM, Sheffield VC (1996) An autosomal recessive nonsyndromic-hearing-loss locus identified by DNA pooling using two inbred Bedouin kindreds. Am J Hum Genet 59:385-391.

Sirmaci A, Duman D, Ozturkmen-Akay H, Erbek S, Incesulu A, Ozturk-Hismi B, Arici ZS, Yuksel-Konuk EB, Tasir-Yilmaz S, Tokgoz-Yilmaz S, Cengiz FB, Aslan I, Yildirim M, Hasanefendioglu-Bayrak A, Aycicek A, Yilmaz I, Fitoz S, Altin F, Ozdag H, Tekin M. (2009) Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations. Int J Pediatr Otorhinolaryngol 73:699-705.

Tlili A, Al Mutery A, Kamal Eddine Ahmad Mohamed W, Mahfood M, Hadj Kacem H (2017a) Prevalence of GJB2 Mutations in Affected Individuals from United Arab Emirates with Autosomal Recessive Nonsyndromic Hearing Loss. Genet Test Mol Biomarkers 21:686-691.

Tlili A, Fahd Al Mutery A, Mahfood M, Kamal Eddine Ahmad Mohamed W, Bajou K (2017b) Identification of a novel frameshift mutation in the ILDR1 gene in a UAE family, mutations review and phenotype genotype correlation. PLoS One 12:e0185281.

Tlili A, Rebeh IB, Aifa-Hmani M, Dhouib H, Moalla J, Tlili-Chouchène J, Said MB, Lahmar I, Benzina Z, Charfedine I, Driss N, Ghorbel A, Ayadi H, Masmoudi S. (2008) TMC1 but not TMC2 is responsible for autosomal recessive nonsyndromic hearing impairment in Tunisian families. Audiol Neurootol 13:213-218.

Vreugde S, Erven A, Kros CJ, Marcotti W, Fuchs H, Kurima K, Wilcox ER, Friedman TB, Griffith AJ, Balling R, Hrabé De Angelis M, Avraham KB, Steel KP. (2002) Beethoven, a mouse model for dominant, progressive hearing loss DFNA36. Nat Genet 30:257-258.

Wang X, Wang L, Peng H, Yang T, Wu H. (2018) A Novel p.G141R Mutation in ILDR1 Leads to Recessive Nonsyndromic Deafness DFNB42 in Two Chinese Han Families. Neural Plast 2018:7272308.

Yang T, Wei X, Chai Y, Li L, Wu H. (2013) Genetic etiology study of the non-syndromic deafness in Chinese Hans by targeted next-generation sequencing. Orphanet J Rare Dis 8:85-1172-8-85.

Published
2018-12-31
How to Cite
[1]
Alobathani, M., Al Mutery, A., Mohamed, W.K.E.A. and Tlili, A. 2018. Identification of nonsense mutation in TMC1 gene inducing hearing loss by clinical exome sequencing. Journal of Biological Sciences and Medicine. 4, 4 (Dec. 2018).
Section
Research Articles