RESUMEN
Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A-->G is the most prevalent in all populations tested so far. Recently, the 1494C-->T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C-->T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C-->T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups (H, U5b, U6a). The study results further support the pathogenic role of 1494C-->T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds.
Asunto(s)
Genes Mitocondriales , Pérdida Auditiva Bilateral/genética , Pérdida Auditiva Sensorineural/genética , ARN Ribosómico/genética , Adulto , Edad de Inicio , Anciano , Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Niño , Femenino , Pruebas Genéticas , Pérdida Auditiva Bilateral/diagnóstico , Pérdida Auditiva Bilateral/tratamiento farmacológico , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Humanos , Patrón de Herencia , Masculino , Persona de Mediana Edad , Linaje , Mutación Puntual , ARN Ribosómico/química , Análisis de Secuencia de ADN , EspañaRESUMEN
We report an infant with auditory neuropathy secondary to the Q829X mutation in the gene encoding otoferlin (OTOF). Included in a universal newborn hearing screening program, the subject passed the otoacoustic emission (OAEs) test. Given that the infant had a familial history of deafness auditory brainstem response (ABR) testing was performed, revealing a profound hearing impairment. The genetic study confirmed that the subject was homozygous for the Q829X mutation in OTOF. The patient underwent a cochlear implant, obtaining satisfactory results. The moderately high prevalence of this mutation in the Spanish population could produce a significant false negative rate in newborn hearing screening programs using OAEs.
Asunto(s)
Nervio Coclear , Pérdida Auditiva/genética , Proteínas de la Membrana/genética , Mutación , Enfermedades del Nervio Vestibulococlear/genética , Humanos , Lactante , MasculinoRESUMEN
Presentamos el caso de un niño con neuropatía auditiva secundaria a la mutación Q829X en el gen de la otoferlina (OTOF). Dentro de un programa universal de detección precoz de hipoacusia en neonatos, el paciente pasó la prueba realizada mediante otoemisiones acústicas (OEAs). Al existir antecedentes familiares de sordera, se realizaron potenciales evocados auditivos del tronco cerebral (PEATC), mediante los cuales se le diagnosticó una pérdida auditiva profunda. El estudio genético confirmó que el paciente era homocigoto para la mutación Q829X en OTOF. El paciente ha seguido tratamiento con implante coclear obteniéndose resultados satisfactorios. La relativa frecuencia de esta mutación en la población española hace que un número no despreciable de casos puedan escapar a la fase de screening mediante OEAs de los programas de detección precoz de sorderas
We report an infant with auditory neuropathy secondary to the Q829X mutation in the gene encoding otoferlin (OTOF). Included in a universal newborn hearing screening program, the subject passed the otoacoustic emission (OAEs) test. Given that the infant had a familial history of deafness auditory brainstem response (ABR) testing was performed, revealing a profound hearing impairment. The genetic study confirmed that the subject was homozygous for the Q829X mutation in OTOF. The patient underwent a cochlear implant, obtaining satisfactory results. The moderately high prevalence of this mutation in the Spanish population could produce a significant false negative rate in newborn hearing screening programs using OAEs
Asunto(s)
Masculino , Lactante , Humanos , Pérdida Auditiva/genética , Nervio Coclear , Proteínas de la Membrana/genética , Mutación , Enfermedades del Nervio Vestibulococlear/genéticaRESUMEN
Introducción: Las mutaciones responsables de hipoacusia no sindrómica que se han encontrado con mayor frecuencia en la población española son la mutación 35delG en el gen de la conexina 26 (GJB2), la deleción del(GJB6- D13S1830) en el gen de la conexina 30 (GJB6), la mutación Q829X en el gen de la otoferlina (OTOF) y la mutación A1555G en el gen del ARN ribosómico (ARNr) 12S del genoma mitocondrial. Pacientes y métodos: Se determinó la presencia de estas mutaciones en 38 pacientes de Cantabria con hipoacusia neurosensorial no sindrómica de inicio congénito o en la infancia. Resultados: Se detectó la mutación A1555G en homoplasmia en 9 pacientes (23,7%). Presentaban la mutación 35delG en heterozigosis 3 individuos (7,9%). Se encontró la deleción del(GJB6-D13S1830) en heterozigosis en un caso (2,6%). Era portador en homozigosis de la mutación Q829X un paciente (2,6%). Conclusiones: Estas cuatro mutaciones están presentes en el 36,8% de los casos de hipoacusia no sindrómica de nuestra muestra
Introduction: The most frequent mutations responsible for non-syndromic hearing impairment in the Spanish population are the 35delG mutation in the connexin 26 gene (GJB2), the del(GJB6-D13S1830) deletion in the connexin 30 gene (GJB6), the Q829X mutation in the otoferlin gene (OTOF), and the A1555G mutation in the 12S rRNA gene of the mitochondrial genome. Patients and methods: Screening for these mutations was performed on 38 patients from Cantabria with non-syndromic sensorineural hearing impairment of congenital/childhood onset. Results: The A1555G mutation was detected in homoplasmy in 9 patients (23,7%). Three individuals were heterozygous for the 35delG mutation (7,9%). The heterozygous del(GJB6-D13S1830) deletion was present in one case (2,6%). One subject was homozygous for the Q829X mutation (2,6%). Conclusions: These four mutations are present in 36,8% of all cases of non-syndromic hearing impairment in our population
Asunto(s)
Niño , Adulto , Anciano , Adolescente , Anciano de 80 o más Años , Humanos , Conexinas/genética , Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/genética , Proteínas de la Membrana/genética , Mutación Puntual/genética , Cromosomas Humanos X/genética , Análisis Mutacional de ADN , Genes de ARNr , HomocigotoAsunto(s)
Conexinas/genética , Pérdida Auditiva/genética , Mutación , Eliminación de Secuencia , Australia/epidemiología , Secuencia de Bases/genética , Bélgica/epidemiología , Brasil/epidemiología , Conexina 26 , Conexina 30 , Análisis Mutacional de ADN , Efecto Fundador , Francia/epidemiología , Frecuencia de los Genes , Haplotipos , Pérdida Auditiva/epidemiología , Humanos , Israel/epidemiología , Italia/epidemiología , España/epidemiología , Reino Unido/epidemiología , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: The most frequent mutations responsible for non-syndromic hearing impairment in the Spanish population are the 35delG mutation in the connexin 26 gene (GJB2), the del(GJB6-D13S1830) deletion in the connexin 30 gene (GJB6), the Q829X mutation in the otoferlin gene (OTOF), and the A1555G mutation in the 12S rRNA gene of the mitochondrial genome. PATIENTS AND METHODS: Screening for these mutations was performed on 38 patients from Cantabria with non-syndromic sensorineural hearing impairment of congenital/childhood onset. RESULTS: The A1555G mutation was detected in homoplasmy in 9 patients (23.7%). Three individuals were heterozygous for the 35delG mutation (7.9%). The heterozygous del(GJB6-D13S1830) deletion was present in one case (2.6%). One subject was homozygous for the Q829X mutation (2.6%). CONCLUSIONS: These four mutations are present in 36.8% of all cases of non-syndromic hearing impairment in our population.