Frecuencia de la mutación p.Q829X del gen Otoferlina (OTOF) en población colombiana con sordera no sindrómica
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Feb 12, 2012
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Introducción: Las pérdidas auditivas son heredables en un 50-60% de los casos. Dentro de estas, las sorderas no sindrómicas predominan y se han descrito más de 40 genes asociados. Uno de los más frecuentemente implicados es el gen de Otoferlina (OTO F).
Objetivo: Determinar la frecuencia de la mutación p.Q829X en el gen OTO F en 649 individuos colombianos con sordera no sindrómica.
Materiales y métodos: Se seleccionó una población de 649 individuos para realizar la búsqueda de la mutación p.Q829X por medio de la técnica PCR-RFLP.
Resultados: Se identificaron 12 individuos con la mutación p.Q829X (12/649), que corresponden a una frecuencia del 1,8%.
Conclusiones:La mutación p.Q829X es la más frecuente en el gen OTO F, y la tercera luego de las mutaciones S199F y 35delG en el gen GJB2, causantes de sordera en la población analizada. Se observó variabilidad en el grado de pérdida auditiva en los individuos homocigotos para la mutación y presencia de neuropatía auditiva en el 62,5% de estos casos.
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References
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2. Kochhar A, Hildebrand MS, Smith RJ. Clinical aspects of hereditary hearing loss. Genet Med. 2007 Jul;9(7):393-408.
3. Houseman MJ, Jackson AP, Al-Gazali LI, Badin RA, Roberts E, Mueller RF. A novel mutation in a family with non-syndromic sensorineural hearing loss that disrupts the newly characterised OTO F long isoforms. J Med Genet. 2001 Aug;38(8):E25.
4. Hutchin T, Coy NN, Conlon H, Telford E, Bromelow K, Blaydon D et al. Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing. Clin Genet. 2005 Dec;68(6):506-12.
5. Marazita ML, Ploughman LM, Rawlings B, Remington E, Arnos KS, Nance WE. Genetic epidemiological studies of earlyonset deafness in the U.S. school-age population. Am J Med Genet. 1993 Jun 15;46(5):486-91.
6. Chaib H, Place C, Salem N, Chardenoux S, Vincent C, Weissenbach J et al. A gene responsible for a sensorineural nonsyndromic recessive deafness maps to chromosome 2p22-23. Hum Mol Genet. 1996 Jan;5(1):155-8.
7. Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N et al. A mutation in OTO F, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet. 1999 Apr;21(4):363-9.
8. Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA, Rodríguez-Ballesteros M, Villamar M, Telleria D et al. Q829X, a novel mutation in the gene encoding otoferlin (OTO F), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. J Med Genet. 2002
Jul;39(7):502-6.
9. Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A et al. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell. 2006 Oct 20;127(2):277-89.
10. Mirghomizadeh F, Pfister M, Apaydin F, Petit C, Kupka S, Pusch CM et al. Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness. Neurobiol Dis. 2002 Jul;10(2):157-64.
11. R odríguez-Ballesteros M, del Castillo FJ, Martín Y, Moreno-Pelayo MA, Morera C, Prieto F et al. Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTO F). Hum Mutat. 2003 Dec;22(6):451-6.
12. Varga R, Kelley PM, Keats BJ, Starr A, Leal SM, Cohn E et al. Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTO F) gene. J Med Genet. 2003 Jan;40(1):45-50.
13. Kapadia S, Lutman ME. Are normal hearing thresholds a sufficient condition for click-evoked otoacoustic emissions? J Acoust Soc Am. 1997 Jun;101(6):3566-7.
14. Kemp DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am. 1978 Nov;64(5):1386-91.
15. Lattig MC, Gélvez N, Plaza SL, Tamayo G, Uribe JI, Salvatierra I et al. Deafness on the island of Providencia - Colombia: different etiology, different genetic counseling. Genet Couns. 2008;19(4):403-12.
16. Tamayo ML, Lattig MC, Plaza SL, Tamayo G, Uribe JI, Bernal JE. Confluencia de sordera no-sindrómica autosómica recesiva y síndrome de Waardenburg en la isla de Providencia-Colombia. Universitas Médica. 1998;39(2):39-43.
17. Tamayo ML, Olarte M, Gélvez N, Gómez M, Frías JL, Bernal JE et al. Molecular studies in the GJB2 gene (Cx26) among a deaf population from Bogota, Colombia: results of a screening program. Int J Pediatr Otorhinolaryngol. 2009 Jan;73(1):97-101.
18. 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 Nov;6(12):2173-7.
19. 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 Apr;62(4):792-9.
20. 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 Jan;106(1):40-4.
21. Del Castillo I, Moreno-Pelayo MA, del Castillo FJ, Brownstein Z, Marlin S, Adina Q et al. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Am J Hum Genet. 2003 Dec;73(6):1452-8.
22. Rodríguez-Ballesteros M, Reynoso R, Olarte M, Villamar M, Morera C, Santarelli R et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTO F) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum Mutat. 2008 Jun;29(6):823-31.
23. Choi BY, Ahmed ZM, Riazuddin S, Bhinder MA, Shahzad M, Husnain T et al. Identities and frequencies of mutations of the otoferlin gene (OTO F) causing DFNB9 deafness in Pakistan. Clin Genet. 2009 Mar;75(3):237-43.
24. del Castillo FJ, Rodríguez-Ballesteros M, Álvarez A, Hutchin T, Leonardi E, de Oliveira CA et al. A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. J Med Genet. 2005 Jul;42(7):588-94.
25. Schug N, Braig C, Zimmermann U, Engel J, Winter H, Ruth P et al. Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat. Eur J Neurosci. 2006 Dec;24(12):3372-80.
26. Putcha GV, Bejjani BA, Bleoo S, Booker JK, Carey JC, Carson N, et al. A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Genet Med. 2007 Jul;9(7):413-26.
27. Longo-Guess C, Gagnon LH, Bergstrom DE, Johnson KR. A missense mutation in the conserved C2B domain of otoferlin causes deafness in a new mouse model of DFNB9. Hear Res. 2007 Dec;234(1-2):21-8.
28. Gallo-Terán J, Megia López R, Morales-Angulo C, del Castillo I, Moreno-Pelayo MA, Mazón Gutiérrez A et al. Evaluation of a family with sensorineural hearing loss due to the Q829X mutation in the OTO F gene. Acta Otorrinolaringol Esp. 2004 Mar;55(3):120-5.
29. Tekin M, Akcayoz D, Incesulu A. A novel missense mutation in a C2 domain of OTO F results in autosomal recessive auditory neuropathy. Am J Med Genet A. 2005 Sep 15;138(1):6-10.
2. Kochhar A, Hildebrand MS, Smith RJ. Clinical aspects of hereditary hearing loss. Genet Med. 2007 Jul;9(7):393-408.
3. Houseman MJ, Jackson AP, Al-Gazali LI, Badin RA, Roberts E, Mueller RF. A novel mutation in a family with non-syndromic sensorineural hearing loss that disrupts the newly characterised OTO F long isoforms. J Med Genet. 2001 Aug;38(8):E25.
4. Hutchin T, Coy NN, Conlon H, Telford E, Bromelow K, Blaydon D et al. Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing. Clin Genet. 2005 Dec;68(6):506-12.
5. Marazita ML, Ploughman LM, Rawlings B, Remington E, Arnos KS, Nance WE. Genetic epidemiological studies of earlyonset deafness in the U.S. school-age population. Am J Med Genet. 1993 Jun 15;46(5):486-91.
6. Chaib H, Place C, Salem N, Chardenoux S, Vincent C, Weissenbach J et al. A gene responsible for a sensorineural nonsyndromic recessive deafness maps to chromosome 2p22-23. Hum Mol Genet. 1996 Jan;5(1):155-8.
7. Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N et al. A mutation in OTO F, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet. 1999 Apr;21(4):363-9.
8. Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA, Rodríguez-Ballesteros M, Villamar M, Telleria D et al. Q829X, a novel mutation in the gene encoding otoferlin (OTO F), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. J Med Genet. 2002
Jul;39(7):502-6.
9. Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A et al. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell. 2006 Oct 20;127(2):277-89.
10. Mirghomizadeh F, Pfister M, Apaydin F, Petit C, Kupka S, Pusch CM et al. Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness. Neurobiol Dis. 2002 Jul;10(2):157-64.
11. R odríguez-Ballesteros M, del Castillo FJ, Martín Y, Moreno-Pelayo MA, Morera C, Prieto F et al. Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTO F). Hum Mutat. 2003 Dec;22(6):451-6.
12. Varga R, Kelley PM, Keats BJ, Starr A, Leal SM, Cohn E et al. Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTO F) gene. J Med Genet. 2003 Jan;40(1):45-50.
13. Kapadia S, Lutman ME. Are normal hearing thresholds a sufficient condition for click-evoked otoacoustic emissions? J Acoust Soc Am. 1997 Jun;101(6):3566-7.
14. Kemp DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am. 1978 Nov;64(5):1386-91.
15. Lattig MC, Gélvez N, Plaza SL, Tamayo G, Uribe JI, Salvatierra I et al. Deafness on the island of Providencia - Colombia: different etiology, different genetic counseling. Genet Couns. 2008;19(4):403-12.
16. Tamayo ML, Lattig MC, Plaza SL, Tamayo G, Uribe JI, Bernal JE. Confluencia de sordera no-sindrómica autosómica recesiva y síndrome de Waardenburg en la isla de Providencia-Colombia. Universitas Médica. 1998;39(2):39-43.
17. Tamayo ML, Olarte M, Gélvez N, Gómez M, Frías JL, Bernal JE et al. Molecular studies in the GJB2 gene (Cx26) among a deaf population from Bogota, Colombia: results of a screening program. Int J Pediatr Otorhinolaryngol. 2009 Jan;73(1):97-101.
18. 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 Nov;6(12):2173-7.
19. 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 Apr;62(4):792-9.
20. 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 Jan;106(1):40-4.
21. Del Castillo I, Moreno-Pelayo MA, del Castillo FJ, Brownstein Z, Marlin S, Adina Q et al. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Am J Hum Genet. 2003 Dec;73(6):1452-8.
22. Rodríguez-Ballesteros M, Reynoso R, Olarte M, Villamar M, Morera C, Santarelli R et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTO F) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum Mutat. 2008 Jun;29(6):823-31.
23. Choi BY, Ahmed ZM, Riazuddin S, Bhinder MA, Shahzad M, Husnain T et al. Identities and frequencies of mutations of the otoferlin gene (OTO F) causing DFNB9 deafness in Pakistan. Clin Genet. 2009 Mar;75(3):237-43.
24. del Castillo FJ, Rodríguez-Ballesteros M, Álvarez A, Hutchin T, Leonardi E, de Oliveira CA et al. A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. J Med Genet. 2005 Jul;42(7):588-94.
25. Schug N, Braig C, Zimmermann U, Engel J, Winter H, Ruth P et al. Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat. Eur J Neurosci. 2006 Dec;24(12):3372-80.
26. Putcha GV, Bejjani BA, Bleoo S, Booker JK, Carey JC, Carson N, et al. A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Genet Med. 2007 Jul;9(7):413-26.
27. Longo-Guess C, Gagnon LH, Bergstrom DE, Johnson KR. A missense mutation in the conserved C2B domain of otoferlin causes deafness in a new mouse model of DFNB9. Hear Res. 2007 Dec;234(1-2):21-8.
28. Gallo-Terán J, Megia López R, Morales-Angulo C, del Castillo I, Moreno-Pelayo MA, Mazón Gutiérrez A et al. Evaluation of a family with sensorineural hearing loss due to the Q829X mutation in the OTO F gene. Acta Otorrinolaringol Esp. 2004 Mar;55(3):120-5.
29. Tekin M, Akcayoz D, Incesulu A. A novel missense mutation in a C2 domain of OTO F results in autosomal recessive auditory neuropathy. Am J Med Genet A. 2005 Sep 15;138(1):6-10.
Como Citar
Morales Ortíz, L., Gelvez Moyano, N., Urrego, L. F., Leiva, M. F., & Tamayo Fernández, M. L. (2012). Frecuencia de la mutación p.Q829X del gen Otoferlina (OTOF) en población colombiana con sordera no sindrómica. Universitas Medica, 53(2), 144–153. https://doi.org/10.11144/Javeriana.umed53-2.fmpg
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