Gennaro Auletta

New evidence for the correlation of the p.G130V mutation in the GJB2 gene and syndromic hearing loss with palmoplantar keratoderma

The GJB2 gene located on chromosome 13q12 and encoding the connexin 26 (Cx26) protein, a transmembrane protein involved in cell–cell attachment of almost all tissues, including the skin, causes autosomal recessive and sometimes dominant nonsyndromic sensorineural hearing loss. GJB2 mutations have also been identified in syndromic disorders exhibiting hearing loss associated with skin problems. Recently, a new mutation, p.G130V in the GJB2 gene has been reported as causative for Vohwinkel syndrome. In this case the p.G130V mutation was found in two patients (son and father) with palmoplantar keratoderma. The father also showed also skin constrictions of the 2nd and 3rd toes of the right foot. Here, we report on another family with palmoplantar keratoderma associated with a dominant form of hearing loss confirming the genotype–phenotype correlation between the mutation p.G130V and the skin abnormalities observed in syndromic disorders with hearing loss as described by [Snoeckx et al. (2005) Hum Mutat 26:60–65].

Identification of a Novel Mutation in the Myosin VIIA Motor Domain in a Family with Autosomal Dominant Hearing Loss (DFNA11)

We ascertained a large Italian family with an autosomal dominant form of non-syndromic sensorineural hearing loss with vestibular involvement. A genome-wide scan found linkage to locus DFNA11. Sequencing of the MYO7A gene in the linked region identified a new missense mutation resulting in an Ala230Val change in the motor domain of the myosin VIIA. Myosin VIIA has already been implicated in several forms of deafness, but this is the third mutation causing a dominant form of deafness, located in the myosin VIIA motor domain in a region never involved in hearing loss until now. A modelled protein structure of myosin VII motor domain provides evidence for a significant functional effect of this missense mutation.

Feasibility and effectiveness of a population-based newborn hearing screening in an economically deprived region of Italy

AIM To describe the effectiveness of a population-based newborn hearing screening program in an economically deprived region of southern Italy. METHODS A screening protocol was proposed for all newborns of the Campania region, starting on January, 2007. For infants identified with hearing loss, information on degree and type of hearing loss and presence of risk factors was collected. RESULTS The infants born in the 3-year study period were 182,188. Among them, 146,026 (80%) were tested with OAE. Sensorineural hearing loss ≥40dBnHL was established for 159 infants (1.1×1000). Among the NICU and WIN infants, the rate of hearing loss was respectively 9×1000 and 0.67×1000. Follow-up information was available for 111 children (70%), as 48 (30%) got care in other regions or health facilities. Most infants were fitted hearing aids by 1 month after diagnosis and 15 children (13.5%) received a cochlear implant at a mean age of 25 months (SD 10). CONCLUSIONS Even in a setting of population poverty, a universal newborn screening program can deliver satisfactory outcomes. The coverage and the tracking system of the program need to be improved, as well as the cooperation between public and private health services.

Middle ear involvement in children with chronic rheumatoid juvenile arthritis

In a selected sample of patients affected by juvenile rheumatoid arthritis (JRA) little is known about middle ear involvement, even though many synovial joints are affected. Multifrequency tympanometry was used to measure admittance, conductance, susceptance and phase angle at different probe frequencies and resonant frequencies. In all, 35 children with JRA and a control group (30 children) were studied. Findings showed that mean resonant frequency values in all children with JRA were greater than in the control children. The multifrequency tympanometry parameters measured in acute JRA subjects are not different from parameters of remission JRA subjects except for a change in the phase angle. The changes found are due to involvement of the incudomalleolar and incudostapedial joints. and incudostapedial joints.

Screening for GJB2 and GJB6 gene mutations in patients from Campania region with sensorineural hearing loss

Abstract The aim of this study was to screen 349 patients affected by sensorineural hearing loss (SNHL), mostly from the Campania region (southern Italy), for GJB2 gene mutations and for two deletions of the GJB6 gene (del GJB6 -D13S1830 and del GJB6 -D13S1854). We identified pathogenetic GJB2 mutations in 51 cases (15% of patients). No GJB6 mutation was found. We also examined the audiologic features of the patients for whom we had an etiologic diagnosis, in order to identify correlations between the severity of hearing loss and the type of mutation. Sumario El objetivo de este estudio fue evaluar 349 pacientes afecta-dos de una hipoacusia sensorineural (SNHL), sobre todo de la región de Campania (Italia del sur), buscando muta-ciones en el gen GJB2 y dos deleciones en el gen GJB6 (del GJB6-D13S1830 y del GJB6-13S1854). Identifica-mos mutaciones patogénicas en 51 pacientes (15% de los pacientes). No se encontraron mutaciones del gen GJB6. También examinamos los rasgos audiológicos de aquellos pacientes de quienes teníamos diagnóstico etiológico, para identificar correlaciones entre la severidad de la pérdida audi-tiva y el tipo de mutación.

Mutational analysis for GJB2, GJB6, and GJB3 genes in Campania within a universal neonatal hearing screening programme

Abstract Objective: To determine the incidence of GJB2 and GJB3 mutations and of two deletions upstream of the GJB6 gene in infants of the Campania region of southern Italy. Design: DNA samples from non-syndromic hearing-impaired infants enrolled in a neonatal screening programme for sensorineural hearing loss were analysed by PCR and by direct sequencing. The audiological features of infants with biallelic GJB2 mutations were also examined to identify genotype-phenotype correlations. Study sample: Molecular analyses were carried out in 129 affected and five unaffected infants. Results: A genetic etiology of hearing loss was identified in 28% of infants, including several at environmental risk of hearing loss. Neither GJB6 nor GJB3 (a gene not previously investigated in the Campania population) mutations were found. Conclusions: This study confirms the importance of universal neonatal hearing screening. The identification of a genetic cause in infants at environmental risk indicates that such infants should be included when investigating etiology. We confirm that also in our geographical area, c.35delG homozygotes tend to have severe symmetrical hearing loss, whereas hearing impairment is milder in compound heterozygotes. Sumario Objetivo: Determinar la incidencia de mutaciones GJB2 y GJB3 y de dos deleciones corriente arriba en el gen GJB6 en niñosde la región de Campania en el sur de Italia. Diseño: Se analizaron por PCR y por secuenciación directa muestras de ADN de niños con trastornos auditivos no sindrómicos incluidos en el programa de tamiz neonatal para hipoacusias sensorineurales. Los rasgos audiológicos de niños con mutaciones bi-alélicas del GJB2 también se examinaron para identificar correlaciones genotípicas y fenotípicas. Muestra del Estudio: Se realizó un análisis molecular en 129 niños afectados y en 5 no afectados. Resultados: Se identificó una etiología genética de la sordera en 28% de los infantes, incluyendo varios con riesgo ambiental de hipoacusia. No se encontraron mutaciones en el gen GJB6 o en el GJB3 (un gene no investigado previamente en la población de Campania). Conclusiones: Este estudio confirma la importancia del tamiz auditivo neonatal universal. La identificación de una causa genética en niños con un riesgo ambiental indica que tales infantes deberían incluirse cuando se investiga la etiología. Confirmamos que también en nuestra área geográfica, los homocigotos c.35delG tienden a tener hipoacusias simétricas severas, mientras que el trastorno auditivo es más leve en heterocigotos compuestos.

Otosclerosis: exclusion of linkage to the OTSC1 and OTSC2 loci in four Italian families.

Otosclerosis is the single most common cause of hearing impairment among adult Caucasians. Little is known about its aetiology and its molecular aspects. Until now, genetic linkage in Otosclerosis has been demonstrated in an Indian family and a Belgian family, showing the presence of two Otosclerosis loci, OTSC1 and OTSC2, respectively. Linkage analysis has never been applied to Italian otosclerotic families. We have collected four multigenerational Italian otosclerotic families that show dominant transmission for the pathology. Here, we report a detailed audiological analysis of these families and a genetic linkage study on the OTSC1 and OTSC2 loci. Statistical analysis revealed the absence of linkage between the disease in our families and the OTSC1 and OTSC2 loci. These data strongly suggest the presence of one or more additional loci for Otosclerosis, which still need to be defined. Sumario La otocsclerosis es la causa mas comun de problemas auditivos entre los adullos caucásicos. Poco se conoce acerca de su etiología y de sus aspectos moleculares. Hasta ahora, los enlaces genéticos en la Otoesclerosis han sido demostrados en familias de la India y Bélgica mostrando la prescncia de dos loci de Otoesclerosis, OTSC1 y ORSC2, respectivamente. Nunca se ha realizado el análisis de enlaces en familias con otoeselerosis en Italia. Nosotros coleclamos los datos multigeneracionales de cuatro familias italianas con Otoesclerosis, que mostraron transmisión dominante de esa patologia. En este trabajo reportamos el análisis audiológico detallado de estas familias y el estudio de enlaces genéticos con los loci OTSC1 y ORSC2. El análisis estadistico reveló la auscncia de relación entre la enfermedad en las cuatro familias y los loci OTSC1 y OTSC2. Estos datos sugieren fuertemente la presencia de uno o más loci adicionales para la Otoesclerosis, que aún es necesario definir.

Phenotypic and genetic characterization of a family carrying two Xq21.1-21.3 interstitial deletions associated with syndromic hearing loss

BackgroundSensorineural hearing impairment is a common pathological manifestation in patients affected by X-linked intellectual disability. A few cases of interstitial deletions at Xq21 with several different phenotypic characteristics have been described, but to date, a complete molecular characterization of the deletions harboring disease-causing genes is still missing. Thus, the aim of this study is to realize a detailed clinical and molecular analysis of a family affected by syndromic X-linked hearing loss with intellectual disability.ResultsClinical analyses revealed a very complex phenotype that included inner ear malformations, vestibular problems, choroideremia and hypotonia with a peculiar pattern of phenotypic variability. Genomic analysis revealed, for the first time, the presence of two close interstitial deletions in the Xq21.1-21.3, harboring 11 protein coding, 9 non-coding genes and 19 pseudogenes. Among these, 3 protein coding genes have already been associated with X-linked hearing loss, intellectual disability and choroideremia.ConclusionsIn this study we highlighted the presence of peculiar genotypic and phenotypic details in a family affected by syndromic X-linked hearing loss with intellectual disability. We identified two, previously unreported, Xq21.1-21.3 interstitial deletions. The two rearrangements, containing several genes, segregate with the clinical features, suggesting their role in the pathogenicity. However, not all the observed phenotypic features can be clearly associated with the known genes thus, further study is necessary to determine regions involved.

SLC26A4 genotypes associated with enlarged vestibular aqueduct malformation in south Italian children with sensorineural hearing loss

aAnnamaria Franzè and Gabriella Esposito are co-first authors. *Corresponding authors: Elio Marciano, Area di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche,Via Sergio Pansini, Università di Napoli Federico II, Italy, Via Sergio Pansini 5, 80131 Naples, Italy, Phone: +39 081 746 3875, Fax: +39 081 746 3581, E-mail: marciano@unina.it; and Francesco Salvatore, CEINGEBiotecnologie Avanzate s.c. a r.l., Via Gaetano Salvatore 486, 80145 Napoli, Italy; IRCCS Fondazione SDN, Naples, Italy, Phone: +39 081 746 3133, Fax: +39 081 746 3650, E-mail: salvator@unina.it Annamaria Franzè: CEINGE-Biotecnologie Avanzate s.c. a r.l., Napoli, Italy; and Area di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli Federico II, Naples, Italy Gabriella Esposito: CEINGE-Biotecnologie Avanzate s.c. a r.l., Napoli, Italy; and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy Carmela Di Domenico, Sandra Iossa and Giuliana Sauchelli: CEINGEBiotecnologie Avanzate s.c. a r.l., Naples, Italy Tiziana Fioretti: IRCCS Fondazione SDN, Naples, Italy Michele Cavaliere: UOC, Otorinolaringoiatria, Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli Federico II, Naples, Italy Gennaro Auletta, Virginia Corvino, Carla Laria and Rita Malesci: Area di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli Federico II, Naples, Italy Letter to the Editor

Multicentre evaluation of the Naída CI Q70 sound processor: feedback from cochlear implant users and professionals

The aim of this survey was to gather data from both implant recipients and professionals on the ease of use of the Naída CI Q70 (Naída CI) sound processor from Advanced Bionics and on the usefulness of the new functions and features available. A secondary objective was to investigate fitting practices with the new processor. A comprehensive user satisfaction survey was conducted in a total of 186 subjects from 24 centres. In parallel, 23 professional questionnaires were collected from 11 centres. Overall, there was high satisfaction with the Naída CI processor from adults, children, experienced and new CI users as well as from professionals. The Naída CI processor was shown as being easy to use by all ages of recipients and by professionals. The majority of experienced CI users rated the Naída CI processor as being similar or better than their previous processor in all areas surveyed. The Naída CI was recommended by the professionals for fitting in all populations. Features like UltraZoom, ZoomControl and DuoPhone would not be fitted to very young children in contrast to adults. Positive ratings were obtained for ease of use, comfort and usefulness of the new functions and features of the Naída CI sound processor. Seventy-seven percent of the experienced CI users rated the new processor as being better than their previous sound processor from a general point of view. The survey also showed that fitting practices were influenced by the age of the user.