Las variantes en el gen RIPOR2 relacionadas con la hipoacusia son infrecuentes en el Norte de España
Resumen Introducción y objetivo: Evaluar la prevalencia y caracterización clínica de las variantes en el gen RIPOR2 en pacientes con hipoacusia neurosensorial (HNS) bilateral de etiología desconocida en el norte de España. Método: Estudio observacional, retrospectivo y descriptivo realizado durante siete años (2018–2024), que incluyó pacientes con HNS bilateral atendidos en un hospital terciario. Se realizó un análisis genético mediante secuenciación de nueva generación (next-generation sequencing, NGS), utilizando un panel de genes para hipoacusia neurosensorial. Se analizó específicamente la presencia de variantes en el gen RIPOR2. Resultados: De los 381 pacientes, se identificaron dos variantes en el gen RIPOR2 en tres individuos (0,8 %): c.1879G>A (p.Asp627Asn) y c.3193G>A (p.Ala1065Thr). La variante c.1879G>A se detectó en dos pacientes, mientras que la variante c.3193G>A se encontró en un solo paciente, quien además presentaba otras variantes patogénicas asociadas con la hipoacusia. Los tres pacientes mostraron una pérdida auditiva en forma de "cookie-bite", afectando predominantemente las frecuencias de 1000, 2000 y 4000 Hz, sin síntomas vestibulares asociados. Conclusiones: Las variantes del gen RIPOR2 en pacientes con HNS en el norte de España (Cantabria) son poco frecuentes. Además, no existe evidencia concluyente que respalde su patogenicidad en casos de HNS de etiología desconocida. Se requieren más estudios para esclarecer su significado clínico.
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Lu Z, Ding Y, Cao W, Wang S, Gao K. Role of RHO family interacting cell polarization regulators (RIPORs) in health and disease: Recent advances and prospects. Int J Biol Sci. 2022;18(2):800-8. https://doi.org/10.7150/ijbs.65457.
Diaz-Horta O, Subasioglu-Uzak A, Grati M, DeSmidt A, Foster J 2nd, Cao L, et al. FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing. Proc Natl Acad Sci U S A. 2014;111(27):9864-8. https://doi.org/10.1073/pnas.1322632111.
Zhao B, Wu Z, Muller U. Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. eLife. 2016;5:e14222. https://doi.org/10.7554/eLife.14222.
Goutman JD, Elgoyhen AB, Gomez-Casati ME. Cochlear hair cells: The sound-sensing machines. FEBS Lett. 2015;589(22):3354-61. https://doi.org/10.1016/j.febslet.2015.09.004.
Manor U, Kachar B. Dynamic length regulation of sensory stereocilia. Semin Cell Dev Biol. 2008;19(6):502-10. https://doi.org/10.1016/j.semcdb.2008.09.005.
Diaz-Horta O, Abad C, Cengiz FB, Bademci G, Blackwelder P, Walz K, et al. Ripor2 is involved in auditory hair cell stereociliary bundle structure and orientation. J Mol Med (Berl). 2018;96(11):1227-38. https://doi.org/10.1007/s00109-018-1704-6.
de Bruijn SE, Smits JJ, Liu C, Lanting CP, Beynon AJ, Blankevoort J, et al. A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss. J Med Genet. 2020 Jul 6;57(12):861-7. https://doi.org/10.1136/jmedgenet-2020-106863.
Velde HM, Homans NC, Goedegebure A, Lanting CP, Pennings RJE, Kremer HJ. Analysis of Rotterdam Study cohorts confirms a previously identified RIPOR2 in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands. J Med Genet. 2023;60(11):1061-6. https://doi.org/10.1136/jmg-2023-109146.
Mardakheh FK, Self A, Marshall CJ. Rho binding to FAM65A regulates Golgi reorientation during cell migration. J Cell Sci. 2016;129(24):4466-79. https://doi.org/10.1242/jcs.196717.
Hermjakob H, Montecchi-Palazzi L, Lewington C, Mudali S, Kerrien S, Orchard S, et al. IntAct: an open source molecular interaction database. Nucleic Acids Res. 2004;32(Database issue):D452-5. https://doi.org/10.1093/nar/gkh052.
Li J, Liu C, Müller U, Zhao B. RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss. Dev Cell. 2022 Sep 26;57(18):2204-20.e6. https://doi.org/10.1016/j.devcel.2022.08.011.
Bischoff AM, Huygen PL, Kemperman MH, Pennings RJ, Bom SJ, Verhagen WI, et al. Vestibular deterioration precedes hearing deterioration in the P51S COCH mutation (DFNA9): an analysis in 74 mutation carriers. Otol Neurotol. 2005 Sep;26(5):918-25. https://doi.org/10.1097/01.mao.0000185048.84641.e3.
Alonso AV, Aguado RG, Camerano AM, Enseñat JF, de la Fuente EO, Angulo CM. Hearing and vestibular impairment related to a variant (c.263G>C) of the COCH gene. Otolaryngol Head Neck Surg. 2024 Dec 12. https://doi.org/10.1002/ohn.1074. Epub ahead of print.
International Organization for Standardization (ISO 7029:2017). Edition 3, 2017 [Internet]. Available from: https://www.iso.org/standard/42916.html
Degree of hearing loss. American Speech-Language-Hearing Association [Internet]. [cited 2024 Aug 14]. Available from: https://www.asha.org/public/hearing/degree-of-hearing-loss
Li MM, Tayoun AA, DiStefano M, et al. ACMG Professional Practice and Guidelines Committee. Clinical evaluation and etiologic diagnosis of hearing loss: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2022;24(7):1392-406. https://doi.org/10.1016/j.gim.2022.03.018.
González-Aguado R, Gallo-Terán J, Onecha E, Morales-Angulo C. Cochleo-vestibular phenotype in patients with pathogenic variations in the ACTG1 gene. Acta Otorrinolaringol Esp. 2024. In press.
Kim SY, Kim BJ, Oh DY, et al. Improving genetic diagnosis by disease-specific, ACMG/AMP variant interpretation guidelines for hearing loss. Sci Rep. 2022;12(1):12457. https://doi.org/10.1038/s41598-022-16661-x.
Usami S, Nishio S. The genetic etiology of hearing loss in Japan revealed by the social health insurance-based genetic testing of 10K patients. Hum Genet. 2022;141(5-6):665-81. https://doi.org/10.1007/s00439-021-02371-3.
Aliazami F, Gilani S, Farhud D, Naraghi M, Afshari M, Eslami M. Epidemiology, etiology, genetic variants in non-syndromic hearing loss in Iran: A systematic review and meta-analysis. Int J Pediatr Otorhinolaryngol. 2023;168:111512. https://doi.org/10.1016/j.ijporl.2023.111512.
Reda del Barrio S, García Fernández A, Quesada-Espinosa JF, et al. Genetic diagnosis of childhood sensorineural hearing loss. Acta Otorrinolaringol Esp. 2024;75(2):83-93. https://doi.org/10.1016/j.otoeng.2023.09.005.
Reda Del Barrio S, de Vergas Gutiérrez J, Quesada-Espinosa JF, et al. Diagnostic yield of genetic testing in adults with sensorineural hearing loss. Acta Otorrinolaringol Esp. 2024;10:S2173-5735(24)00026-7. https://doi.org/10.1016/j.otoeng.2023.10.007.
Cabanillas R, Diñeiro M, Cifuentes GA, et al. Comprehensive genomic diagnosis of nonsyndromic and syndromic hereditary hearing loss in Spanish patients. BMC Med Genomics. 2018;11:58. https://doi.org/10.1186/s12920-018-0375-5.
Del Castillo I, Morín M, Domínguez Ruiz M, Moreno Pelayo MA. Genetic etiology of non-syndromic hearing loss in Europe. Hum Genet. 2022;141(5-6):683-96. https://doi.org/10.1007/s00439-021-02425-6.
Seligman KL, Shearer AL, Frees K, Nishimura C, Kolbe D, Dunn C, et al. Genetic causes of hearing loss in a large cohort of cochlear implant recipients. Otolaryngol Head Neck Surg. 2022;166(4):734-7. https://doi.org/10.1177/01945998211021308.
Diaz-Horta O, Subasioglu-Uzak A, Grati M, DeSmidt A, Foster J 2nd, Cao L, et al. FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing. Proc Natl Acad Sci U S A. 2014;111(27):9864-8. https://doi.org/10.1073/pnas.1322632111.
Zhao B, Wu Z, Muller U. Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. eLife. 2016;5:e14222. https://doi.org/10.7554/eLife.14222.
Goutman JD, Elgoyhen AB, Gomez-Casati ME. Cochlear hair cells: The sound-sensing machines. FEBS Lett. 2015;589(22):3354-61. https://doi.org/10.1016/j.febslet.2015.09.004.
Manor U, Kachar B. Dynamic length regulation of sensory stereocilia. Semin Cell Dev Biol. 2008;19(6):502-10. https://doi.org/10.1016/j.semcdb.2008.09.005.
Diaz-Horta O, Abad C, Cengiz FB, Bademci G, Blackwelder P, Walz K, et al. Ripor2 is involved in auditory hair cell stereociliary bundle structure and orientation. J Mol Med (Berl). 2018;96(11):1227-38. https://doi.org/10.1007/s00109-018-1704-6.
de Bruijn SE, Smits JJ, Liu C, Lanting CP, Beynon AJ, Blankevoort J, et al. A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss. J Med Genet. 2020 Jul 6;57(12):861-7. https://doi.org/10.1136/jmedgenet-2020-106863.
Velde HM, Homans NC, Goedegebure A, Lanting CP, Pennings RJE, Kremer HJ. Analysis of Rotterdam Study cohorts confirms a previously identified RIPOR2 in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands. J Med Genet. 2023;60(11):1061-6. https://doi.org/10.1136/jmg-2023-109146.
Mardakheh FK, Self A, Marshall CJ. Rho binding to FAM65A regulates Golgi reorientation during cell migration. J Cell Sci. 2016;129(24):4466-79. https://doi.org/10.1242/jcs.196717.
Hermjakob H, Montecchi-Palazzi L, Lewington C, Mudali S, Kerrien S, Orchard S, et al. IntAct: an open source molecular interaction database. Nucleic Acids Res. 2004;32(Database issue):D452-5. https://doi.org/10.1093/nar/gkh052.
Li J, Liu C, Müller U, Zhao B. RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss. Dev Cell. 2022 Sep 26;57(18):2204-20.e6. https://doi.org/10.1016/j.devcel.2022.08.011.
Bischoff AM, Huygen PL, Kemperman MH, Pennings RJ, Bom SJ, Verhagen WI, et al. Vestibular deterioration precedes hearing deterioration in the P51S COCH mutation (DFNA9): an analysis in 74 mutation carriers. Otol Neurotol. 2005 Sep;26(5):918-25. https://doi.org/10.1097/01.mao.0000185048.84641.e3.
Alonso AV, Aguado RG, Camerano AM, Enseñat JF, de la Fuente EO, Angulo CM. Hearing and vestibular impairment related to a variant (c.263G>C) of the COCH gene. Otolaryngol Head Neck Surg. 2024 Dec 12. https://doi.org/10.1002/ohn.1074. Epub ahead of print.
International Organization for Standardization (ISO 7029:2017). Edition 3, 2017 [Internet]. Available from: https://www.iso.org/standard/42916.html
Degree of hearing loss. American Speech-Language-Hearing Association [Internet]. [cited 2024 Aug 14]. Available from: https://www.asha.org/public/hearing/degree-of-hearing-loss
Li MM, Tayoun AA, DiStefano M, et al. ACMG Professional Practice and Guidelines Committee. Clinical evaluation and etiologic diagnosis of hearing loss: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2022;24(7):1392-406. https://doi.org/10.1016/j.gim.2022.03.018.
González-Aguado R, Gallo-Terán J, Onecha E, Morales-Angulo C. Cochleo-vestibular phenotype in patients with pathogenic variations in the ACTG1 gene. Acta Otorrinolaringol Esp. 2024. In press.
Kim SY, Kim BJ, Oh DY, et al. Improving genetic diagnosis by disease-specific, ACMG/AMP variant interpretation guidelines for hearing loss. Sci Rep. 2022;12(1):12457. https://doi.org/10.1038/s41598-022-16661-x.
Usami S, Nishio S. The genetic etiology of hearing loss in Japan revealed by the social health insurance-based genetic testing of 10K patients. Hum Genet. 2022;141(5-6):665-81. https://doi.org/10.1007/s00439-021-02371-3.
Aliazami F, Gilani S, Farhud D, Naraghi M, Afshari M, Eslami M. Epidemiology, etiology, genetic variants in non-syndromic hearing loss in Iran: A systematic review and meta-analysis. Int J Pediatr Otorhinolaryngol. 2023;168:111512. https://doi.org/10.1016/j.ijporl.2023.111512.
Reda del Barrio S, García Fernández A, Quesada-Espinosa JF, et al. Genetic diagnosis of childhood sensorineural hearing loss. Acta Otorrinolaringol Esp. 2024;75(2):83-93. https://doi.org/10.1016/j.otoeng.2023.09.005.
Reda Del Barrio S, de Vergas Gutiérrez J, Quesada-Espinosa JF, et al. Diagnostic yield of genetic testing in adults with sensorineural hearing loss. Acta Otorrinolaringol Esp. 2024;10:S2173-5735(24)00026-7. https://doi.org/10.1016/j.otoeng.2023.10.007.
Cabanillas R, Diñeiro M, Cifuentes GA, et al. Comprehensive genomic diagnosis of nonsyndromic and syndromic hereditary hearing loss in Spanish patients. BMC Med Genomics. 2018;11:58. https://doi.org/10.1186/s12920-018-0375-5.
Del Castillo I, Morín M, Domínguez Ruiz M, Moreno Pelayo MA. Genetic etiology of non-syndromic hearing loss in Europe. Hum Genet. 2022;141(5-6):683-96. https://doi.org/10.1007/s00439-021-02425-6.
Seligman KL, Shearer AL, Frees K, Nishimura C, Kolbe D, Dunn C, et al. Genetic causes of hearing loss in a large cohort of cochlear implant recipients. Otolaryngol Head Neck Surg. 2022;166(4):734-7. https://doi.org/10.1177/01945998211021308.
Veiga Alonso, A., Fernández Enseñat, J., Martínez Camerano, A., González Aguado, R., Onecha de la Fuente, E., & Morales Angulo, C. (2025). Las variantes en el gen RIPOR2 relacionadas con la hipoacusia son infrecuentes en el Norte de España. Revista ORL, e32877. https://doi.org/10.14201/orl.32877
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