ABSTRACT
BACKGROUND: Keratitis-Ichthyosis-Deafness (KID) syndrome is a rare condition characterized by pre-lingual sensorineural deafness with skin hyperkeratinization. The primary cause of the disease is a loss-of-function mutation in the GJB2 gene. Mutations in Argentinean patients have not been described. CASE PRESENTATION: We studied a 2 year-old boy with bilateral congenital sensorineural deafness with dry skin over the entire body, hypotrichosis of the scalp, thin and light-blond hair. Analysis of the GJB2 gene nucleotide sequence revealed the substitution of guanine-148 by adenine predicted to result in an Asp50Asn amino acid substitution. CONCLUSION: This is the first KID report in a patient from Argentina. This de novo mutation proved to be the cause of keratitis-ichthyosis-deafness syndrome (KID-syndrome) in the patient, and has implications in medical genetic practice.
Subject(s)
Amino Acid Substitution , Connexins/genetics , Keratitis/genetics , Sequence Analysis, DNA/methods , Argentina , Child, Preschool , Connexin 26 , Genetic Predisposition to Disease , Humans , MaleABSTRACT
Mutations in the GJB2 gene are responsible for more than half of all cases of recessive non-syndromic deafness. This article presents a mutation analysis of the GJB2, GJB6, OTOF and MTRNR1 genes in 252 patients with sensorineural non-syndromic hearing loss. Thirty-one different mutations were identified in GJB2 and GJB6 in 86 of the 252 (34%) patients. We describe for the first time two new mutations in GJB2: the missense mutation c.29 T>C (p.Leu10Pro) in the N terminal domain and c.326 G>T (p.Gly109Val) in the intracytoplasmic domain of connexin 26. This work shows the high prevalence of GJB2 mutations in the Argentinean population, with frequencies that are comparable to those of the Mediterranean area. Most important, it adds two novel GJB2 mutations to be taken into consideration in the genetic diagnosis of non-syndromic sensorineural hearing loss.
Subject(s)
Connexins/genetics , Hearing Loss/genetics , Mutation , Polymorphism, Single Nucleotide , Amino Acid Substitution , Argentina , Connexin 26 , DNA Primers , Frameshift Mutation , Genes, Recessive , Genetic Variation , Humans , Introns , Polymerase Chain Reaction/methods , Polymorphism, Genetic , Sequence DeletionABSTRACT
CONCLUSION: There were no apparent differences in speech performance after cochlear implantation between patients with biallelic GJB2 and/or GJB6 mutations and those with deafness of unknown aetiology. These data have important implications for the selection of prognostic indicators of the outcome of cochlear implantation. OBJECTIVE: To compare performance after cochlear implantation in children with mutations in GJB2 (connexin 26) and/or GJB6 (connexin 30) and children with deafness of unknown aetiology. SUBJECTS AND METHODS: Genetic analysis and speech performance evaluation was determined in 24 patients with (n=11) and without (n=13) biallelic GJB2 and/or GJB6 mutations who underwent cochlear implantation. Speech perception skills were measured 12 and 24 months after surgery. Each patient was classified in accordance with the speech perception category (SPC). RESULTS: Overall, the two groups showed similar significant improvement in speech perception after implantation.
Subject(s)
Cochlear Implantation , Connexins/genetics , Deafness/congenital , Speech Perception , Audiometry, Speech , Case-Control Studies , Child, Preschool , Connexin 26 , Connexin 30 , DNA Mutational Analysis , Deafness/surgery , Female , Humans , Infant , Male , MutationABSTRACT
Objetivo: Mostrar los resultados obtenidos mediante el uso del Implante Auditivo de Tronco Cerebral (IATC) en niños con imposibilidad de recibir un implante coclear (IC), con hipoacusia no asociada a Neurofibromatosis tipo II (NFII). Tipo de estudio: Presentación de casos. Material y método: Se muestran los resultados obtenidos en los dos primeros casos en América en niños (3 y 10 años, respectivamente) a los que se les colocó un I A TC por agenesia de nervio y cóclea. Resultados: Se logró niveles de 30db a 40 db en las audiometrías posteriores a la activación en frecuencias de 250-6.000 Hz, lograron detectar el test de Ling en su totalidad, con buena y rápida respuesta al nombre en una situación estructurada y sin pistas visuales dentro del primer mes de activación. Conclusiones: De acuerdo con nuestra reciente experiencia los casos de niños con agenesia de cóclea y/o nervio, pueden ser considerados para la colocación de un IATC porque la anatomía de los núcleos auditivos está intacta.
Aim: To discuss the results obtained with auditory brainstem implant (ABI) in children non-eligible for cochlear implant, presenting with non-NFII related hypoacusia. A case report study. Materials and Method: Two cases are presented, both of children (aged 3 and 10 years old, respectively), who underwent ABI because of nerve and cochlear agenesis Results: Post-implant audiometric levels were 30 to 40 dB for frequencies between 25 and 6000 Hz. Both patients were able to fully detect the Ling sound test with good and fast answers in a structured non-visual cues-situation within the first post-activation month. Conclusions: In our experience, children with nerve and/or cochlear agenesis could be considered for ABS implantation, because the auditory nuclei's anatomy is intact.
Subject(s)
Humans , Child, Preschool , Child , Auditory Brain Stem Implants , Hearing Loss, Bilateral/surgery , Electrodes, Implanted , Acoustic Stimulation , Auditory Brain Stem Implantation , Cochlear Nerve/abnormalities , Cochlear Nerve/surgery , Cochlear Nerve/physiology , Auditory Perception , Hearing Tests , Correction of Hearing Impairment , Treatment Outcome , Patient SelectionABSTRACT
El Implante Auditivo del Tronco Cerebral (IATC) se usa desde 1979 para reestablecer la audición en pacientes con Neurofibromatosis tipo II (NF2) con sordera profunda bilateral, en el momento de la remoción tumoral. Hace 5 años, se comienza a efectuar en adultos y niños con imposibilidad de realizarse un Implante Coclear (IC) por otras causas que no sean NF2. Los resultados auditivos obtenidos por el Dr. Vittorio Colletti, primer autor en realizarlos en todo el mundo, son mejores a los obtenidos con el IATC posterior a la remoción tumoral. Los estudios presentados demuestran que se obtienen resultados significativamente mejores, que en los pacientes implantados con NF-2. Colletti y colaboradores obtuvieron con el IATCen casos no tumorales, un promedio de reconocimiento de oraciones en forma sólo auditiva, sin lectura labial del 63 por ciento. En casos tumorales el promedio es de 12,2 por ciento. Mostrar los resultados mediante el uso del IATC en niños con imposibilidad de recibir un IC, con hipoacusia no asociada a NF2. Presentación de casos. Se muestran los resultados obtenidos en los dos primeros casos en América en niños (2 y 10 años respectivamente) a los que se les colocó IATC por agenesia de nervio y cóclea. Se logró niveles de 30 a 40 db en las audiciometrías posteriores a la activación en frecuencias de 250-6000 Hz, lograron detectar el Test de Ling en su totalidad, con buena y rápida respuesta al nombre en una situación estructurada y sin pistas visuales De acuerdo con nuestra reciente experiencia los casos no tumorales pueden ser considerados para la colocación de un IATC porque la anatomía de los núcleos auditivos está intacta. El impacto de este tipo de implantes en la vida de los pacientes ha resultado muy positivo.
Subject(s)
Humans , Child , Deafness , Ear Neoplasms , Auditory Brain Stem Implants , /pathology , Otolaryngology , VenezuelaABSTRACT
Genetically caused congenital deafness is a common trait affecting 1 in 2000 children and it is predominantly inherited in an autosomal recessive fashion. Several mutations in the GJB2 gene and a deletion of 342 kb in GJB6 (delGJB6-D13S1830) have been identified worldwide in patients with hearing impairment. The aim of this study was to determine the prevalence of these mutations in Argentina. Non-syndromic 46 probands (17 familial and 29 sporadic cases) were genetically evaluated. Mutations in GJB2 and/or delGJB6-D13S1830 were found in 19 patients, accounting for 41.3% of the sample. Of the 46 patients investigated in this study, 12 (26.1%) were diagnosed to carry sequence variations in both alleles; all but one, were considered causative for hearing impairment in those patients. In 7 out of 46 patients (15.2%) only one mutant allele was detected. Of their 38 chromosomes, 71% resulted with mutations in the GJB2 gene and 11% in GJB6. The most frequent mutation in GJB2 (24%) was c.35delG (11% homozygous and 13% heterozygous and compound heterozygous). In addition, 11 sequence variations different from c.35delG, were identified in the coding region of the GJB2 gene: T8M, V27I, M34T, E47X, R75W, W77R, I82M, L90P, E129K, V153I, M163V. The delGJB6-D13S1830 mutation was found in 4 patients (9%), 3 of them associated with GJB2 mutations, resulting in compound heterozygous for the DFNB1 locus. The present study demonstrates that mutations in the GJB2 gene and the delGJB6-D13S1830 are prevalent in the Argentinean population.
