Expertos Invitados





ESTUDO DE MUTAÇOES MITOCONDRIAIS ASSOCIADAS A DEFICIENCIA AUDITIVA SENSORIONEURAL EM PACIENTES BRASILEIROS

(especial para SIIC © Derechos reservados)
Muitas mutações podem contribuir para a presbiacusia e para a deficiência auditiva em geral, e a deleção mitocondrial mtDNA4977 associada a presbiacusia e a mutação mitocondrial A1555G relacionada ao uso de antibióticos aminoglicosídeos, podem ser apenas uma delas.
Autor:
Vânia Belintani piatto
Columnista Experto de SIIC

Institución:
Faculdade De Medicina De São José Do Rio Preto

Artículos publicados por Vânia Belintani piatto
Recepción del artículo
15 de Mayo, 2007 		Aprobación
1 de Agosto, 2007
Primera edición
18 de Octubre, 2007 		Segunda edición, ampliada y corregida
7 de Junio, 2021

ESTUDO DE MUTAÇOES MITOCONDRIAIS ASSOCIADAS A DEFICIENCIA AUDITIVA SENSORIONEURAL EM PACIENTES BRASILEIROS

Resumen
Introdução: A presbiacusia é a causa mais comum de deficiência auditiva, geralmente associada ao envelhecimento e a mutação mitocondrial A1555G é a principal alteração associada a surdez ocasionada pelo uso de aminoglicosídeos. Objetivo: Investigar a prevalência da deleção mitocondrial de 4977 pares de bases em pacientes com presbiacusia e da mutação A1555G em neonatos. Material e métodos: Estudo de casos em cem pacientes com presbiacusia e em cem neonatos com audição normal. O DNA foi extraído de amostras de leucócitos e primers específicos foram designados para amplificar o gene do citocromo b e as regiões que abrangem a deleção de 4 977 pb e a mutação A1555G do DNA mitocondrial, usando a técnica da reação em cadeia da polimerase e do polimorfismo no comprimento de fragmentos de restrição. Resultados: Uma região do gene do citocromo b foi amplificada confirmando a presença do DNA mitocondrial em todas as amostras do estudo. A deleção mitocondrial mtDNA4977 não foi identificada em todos os pacientes com presbiacusia, assim como a mutação A1555G nos neonatos. Conclusões: Estes resultados não descartam a possibilidade da existência de outras mutações que possam ocasionar presbiacusia ou a deficiência auditiva associada ou não ao uso de aminoglicosídeos e reforçam a importância de se identificar as causas genéticas subjacentes a fim de propiciar melhor compreensão das doenças auditivas na população brasileira.

Palabras clave
presbiacusia, deficiência auditiva, aminoglicosídeos, DNA mitocondrial, deleção mtDNA4977, mutação A1555G


Artículo completo
(castellano)
Extensión:  +/-8.12 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Study of Mitochondrial Mutations Associated with Sensorineural Hearing Loss in Brazilian Patients

Abstract
Introduction: Presbycusis -generally associated with aging- is the most frequent cause of hearing loss, and mitochondrial A1555G mutation is the main change associated with deafness caused by the use of aminoglycoside antibiotic. Objective: To investigate the prevalence of mitochondrial 4 977 bp deletion in patients with presbycusis and the prevalence of A1555G mutation in neonates. Material and methods: Case study on one hundred patients with presbycusis and one hundred neonates with normal hearing. DNA was extracted from leukocyte specimens and specific primers were designed to amplify cytochrome b gene and regions including mtDNA 4977 bp deletion and A1555G mutation, by PCR technique and restriction fragment length polymorphism (RFLP) technique. Results: A region of the cytochrome b gene was amplified and the presence of mtDNA was documented in all study specimens. Deletion of mtDNA4977 was not identified in any patient suffering from presbycusis, neither was A155G mutation found in neonates. Conclusions: These results do not allow ruling out the existence of other mutations causing presbycusis or hearing loss, associated or not with the use of aminoglycoside antibiotics, and to reinforce the importance of identifying the underlying genetic causes in order to contribute to a better understanding of hearing loss in the Brazilian population.

Key words
presbyacusis, hearing loss, aminoglycosides, mitochondrial DNA, mtDNA4977 deletion, A1555G mutation

Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Genética Humana
Relacionadas: Bioquímica, Diagnóstico por Laboratorio, Medicina Interna, Neurología, Otorrinolaringología



Comprar este artículo
Extensión: 8.12 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Vânia Belintani Piatto, Faculdade de Medicina de São José do Rio Preto, 15035-180, Rua Santina Figliagi Ceccato 450, AP-23A, São Paulo, Brasil
Patrocinio y reconocimiento:
Agradecemos aos pacientes que sem os seus consentimento e cooperação, este estudo não seria possível. Esta contribuição é extremamente importante para permitir a continuidade das pesquisas científicas a fim de proporcionar um futuro melhor aos brasileiros. Agradecemos a nossa amiga e tradutora Cecília Meneguette Ferreira, por seu considerável auxílio.
Bibliografía del artículo
1. Davis AC. The prevalence of hearing impairment and reported hearing disability among adults in Great Britain. Int J Epidemiol 18:911-7, 1989.
2. Joint Committee on Infant Hearing Year 2000 Position Statement. Principles and guidelines for early hearing detection and intervention programs. www.audiology.org/professional/positions/jcih-early.php, 2006.
3. Morton NE. Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 630:16-31, 1991.
4. Mustafa T, Arnos KS, Pandya A. Advances in hereditary deafness. Lancet 358:1082-1090, 2001.
5. Skvorak Giersch AB, Morton CC. Genetic causes of nonsyndromic hearing loss. Curr Opin Pediatr 11(6):551-557, 1999.
6. Petty RKH, Harding AE, Morgan-Hughes JA. The clinical features of mitochondrial myopathy. Brain 109:915-38, 1986.
7. Nass MM. The circularity of mitochondrial DNA. Proc Natl Acad Sci USA 56:1215-22, 1966.
8. Sinclair JH, Stevens BJ. Circular DNA filaments from mouse mitochondria. Proc Natl Acad Sci USA 56: 208-14, 1966.
9. Van Bruggen EF, Borst P, Ruttenberg GJ, Gruber M, Kroon AM. Circular mitochondrial DNA. Biochim Biophys Acta 119-437-9, 1966.
10. Anderson S, Bankier AT, Barrel BG, Bruijn MHL, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature 290:457-65, 1981.
11. Maillet M. Biologia Celular. São Paulo:Santos, 279-302, 2003.
12. Wallace DC. Diseases of the mitochondrial DNA. Annu Rev Biochem 1175-212, 1992.
13. Hutchin TP, Thompson KR, Newton V, Bitner-Glindzicz M, Mueller RF. Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromal sensorineural hearing impairment. J Med Genet 38:229-31, 2001.
14. Prezant TR, Agapian JV, Bohlman MC, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 4:289-294, 1993.
15. Seidman MD, Khan MJ, Bai UP, et al. The association of mitochondrial DNA deletions and cochlear pathology: a molecular biologic tool. Laryngoscope 106:777-83, 1996.
16. Guan MX, Fischel-Ghodsian N, Attardi G. A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity. Hum Mol Genet 9:1787-1793, 2000.
17. Giordano C, Pallotti F, Walker WF, et al. Pathogenesis of the deafness-associated A1555G mitochondrial DNA mutation. Biochem Biophys Res Commun 293:521-529, 2002.
18. Tamagawa Y, Kitamura K, Ishida T, et al. Mitochondrial DNA mutation at nucleotide 1555 in a patient with bilateral sensorineural hearing loss of unknown etiology. Acta Otolaryngol 116:796-796, 1996.
19. Estivill X, Govea N, Barceló A, et al. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment with aminoglycosides. Am J Hum Genet 62:27-35, 1998.
20. Scrimshaw BJ, Faed JM, Tate WP, Yun K. Rapid identification of an A1555G mutation in human mitochondrial DNA implicated in aminoglycoside-induced ototoxicity. J Hum Genet 44:388-390, 1999.
21. Usami S, Abe S, Akita J, et al. Prevalence of mitochondrial gene mutations among hearing impaired patients. J Med Genet 37:38-40, 2000.
22. Oshima T, Kudo T, Ikeda K. Point mutation of the mitochondrial genome in Japanese deaf-mutism. ORL J Otorhinolaryngol Relat Spec 63:329-332, 2001.
23. Kupka S, Toth T, Wrobel M, Zeissler U, et al. Mutation A1555G in the 12S rRNA gene and its epidemiological importance in German, Hungarian, and Polish patients. Hum Mutat 19:308-309, 2002.
24. Østergaard E, Montserrat-Sentis B, GrønsKov K, Brøndum-Nielsen K. The A1555G mtDNA mutation in Danish hearing-impaired patients: frequency and clinical signs. Clin Genet 62:303-305, 2002.
25. Malik SG, Pieter N, Sudoyo H, Kadir A, Marzuki S. Prevalence of the mitochondrial DNA A1555G mutation in sensorineural deafness in Island Southeast Asia. J Hum Genet 48:180-483, 2003.
26. Tekin M, Duman T, Bogoçlu G, et al. Frequency of mtDNA A1555G and A7445G mutations among children with prelingual deafness in Turkey. Eur J Pediatr 162:154-158, 2003.
27. Iwasaki S, Tamagawa Y, Ocho S, et al. Hereditary sensorineural hearing loss of unknown cause involving mitochondrial DNA 1555 mutation. ORL J Otorhinolaryngol Relat Spec 62:100-103, 2002.
28. Matsunaga T, Kumanomido H, Shiroma M, et al. Deafness due to A1555G mitochondrial mutation without use of aminoglycoside. Laryngoscope 114:1085-1090, 2004.
29. Abreu-Silva RS, LezIrovitz K, Braga MCC, et al. Prevalence of the A1555G (12S rRNA) and tRNASer (UCN) mitochondrial mutations in hearing-impaired Brazilians patients. Braz J Med Biol Res 39:219-226, 2006.
30. Lindane AW, Marzuki S, Ozawa T, et al. Mitochondrial DNA mutations as an important contributor to aging and degenerative diseases. Lancet 1:642-5, 1985.
31. Yen TC, Su JH, King KL. Ageing-associated 5kb deletion in human liver mitochondrial DNA. Biochem Byophys Res Commun 178:124-31, 1991.
32. Cortopassi GA, Arnheim N. Detection of a specific mitochondrial DNA deletion in tissues of older humans. Nucleic Acid Res 18:6927-33, 1990.
33. Seidman MD, Ahmad N, Bai U. Molecular mechanisms of age-related hearing loss. Ageing Res Rev 331-43, 2002.
34. Bai U, Seidman MD, Hinojosa R, Quirk WS. Mitochondrial DNA deletions associated with aging and possibly presbicusis: a human archival temporal bone study. Am J Otol 18:449-53, 1997.
35. Fischel-Ghodsian N, Bykhovskaya Y, Taylor K, Kahen T, Cantor R, Ehrenman K, Smith R, Keithley E. Temporal bone analysis of patients with presbycusis reveals high frequency of mitochondrial mutations. Hear Res 110:147-54, 1997.
36. Ueda N, Oshima T, Ikeda K, Abe K, Aoki M, Takasaka T. Mitochondrial DNA deletions a predisposing cause for sensorineural hearing loss. Laryngoscope 108:580-4, 1998.
37. Han W, Han D, Jiang S. Mitochondrial DNA4977 deletions associated with human presbycusis. Zhonghua Er Bi Yan Za Zhi 35:416-9, 2000.
38. Keithley E, Harris B, Desai K, Linthicum F, Fischel-Ghodsian N. Mitochondrial cytochrome oxidase immunolabeling in aged human temporal bones. Hear Res 157:93-9, 2001.
39. Fischel-Ghodsian N. Mitochondrial deafness. Ear Hear 24:303-13, 2003.
40. Dai P, Yang W, Jiang S, Gu R, Yuan H, Han D, Guo W, Cao J. Correlation of cochlear blood supply with mitochondrial DNA common deletion in presbiacusis. Acta Otolaryngol 124:130-6, 2004.
41. Pickles JO. Mutation in mitochondrial DNA as a cause of presbyacusis. Audiol Neurootol 9:23-33, 2004.
42. Seidman MD, Ahmad N, Joshi D, Seidman J, Thawani S, Quirk WS. Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage. Acta Otolaryngol 552:16-24, 2004.
43. Noguchi Y, Yashima T, Ito T et al. Audiovestibular findings in patients with mitochondrial A1555G mutation. Laryngoscope 114:344-8, 2004.
44. Andrews RM, Kubacha I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet 23:147, 1999.
45.Oshima T, Ueda N, Ikeda K, Abe K, Takasaka T. Bilateral sensorineural hearing loss associated with the point mutation in the mitochondrial genome. Laryngoscope 106:43-8, 1996.
46. Keithley EM, Ryan AF, Feldman ML. Cochlear degeneration in aged rats of four strains. Hear Res 59, 171-178, 1992.
47. Zhang C, Baumer A, Maxwell RJ, Linnane AW, Nagley P. Multiple mitochondrial DNA deletions in an elderley human individual. FEBS Lett 297:34-8, 1992.
48. Belintani Piatto V, Maria Goloni Bertollo E, Lúcia Sartorato E, Victor Maniglia J. Prevalence of the GJB2 mutations and the del(GJB6-D13S1830) mutation in Brazilian patients with deafness. Hear Res 196:87-93, 2004.
49. Tekin M, Akar N, Cin S, et al. Connexin 26 (GJB2) mutations in the Turkish population: implications for the origin and high frequency of the 35 delG mutation in Caucasians. Human Genet 108:385-9, 2001.
50. Abe S, Usami S, Shinkawa H, Kelley PM, Kimberling WJ. Prevalent connexin 26 gene (GJB2) mutations in Japanese. J Med Genet 37:41-3, 2000.
51. Pandya A, Tekin M, Erdenetungalag R, et al. A unique spectrum of alterations in the Cx26 gene in deaf probands from Mongolia. Eur J Hum Genet 9:388, 2001.
52. Matsunaga T Kumanomido H, Shiroma M, Goto Y, Usami S. Audiological features and mitochondrial DNA sequence in a large family carrying mitochondrial A1555G mutation without use of aminoglycoside. Ann Otol Rhinol Laryngol 114:153-60, 2005.
53. Pandya A, Xia X, Radnaabazar J, Batsuuri J, Dangaansuren B, Fischel-Ghodsian N, Nance WE. Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J Med Genet 34:169-72, 1997.
54. Gardner JC, Goliath R, Viljoen D, et al. Familial streptomycin ototoxicity in a South African family: a mitochondrial disorder. J Med Genet 34:904-6, 1997.
55. Hutchin T, Cortopassi G. Mitochondrial DNA haplotype predicts deafness risk. Am J Med Genet 60:592, 1995.
56. Usami S, Abe S, Kasai M, et al. Genetic and clinical features of sensorineural hearing loss associated with the 1555 mitochondrial mutation. Laryngoscope 107:438-90, 1997.
57. Kleomitis E, Iliadis T, Voyiatzis N, et al. Analysis of the A1555G mtDNA mutation in Greek patients with sensorineural deafness. Am J Hum Genet 67:1879, 2000.
58. Tang HY, Hutcheson E, Neil S Drummond-Borg M, Sper M, Alford RL. Genetic susceptibility to aminoglycoside ototoxicity: How many are at risk? Genet Med 4:336-45, 2002.
59. Dent KM, Kenneson A, Palumbos JC, et al. Methodology of a multistate study of congenital hearing loss: preliminary data from Utah newborn screening. Am J Med Genet C Semin Med Genet 125:28-34, 2004.
60. Gravina LP, Foncuberta ME, Estrada RC, Barreiro C, Chertkoff L. Carrier frequency of the 35delG and A1555G deafness mutations in the Argentinean population impact on the newborn hearing screening. Int J Pediatr Otorhinolaryngol 4:639-43, 2007.
 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
Inicio/Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008