Beatriz Arellano

Heteroplasmy for the 1555A>G mutation in the mitochondrial 12S rRNA gene in six Spanish families with non-syndromic hearing loss

Hearing impairment is the most prevalent sensory disorder and genetic causes are thought to be responsible for over 60% of the cases in developed countries.1 Inherited hearing impairment is highly heterogeneous from both the clinical and genetic points of view.1,2 It varies in age of onset, severity, and audiological characteristics, and it can be associated or not with other clinical features (syndromic or non-syndromic hearing impairment). Genetic transmission includes autosomal (dominant and recessive), X linked, and maternal inheritance patterns. This unparalleled heterogeneity is well illustrated by the fact that over 70 loci in the nuclear genome have been reported to be involved in non-syndromic hearing impairment, and about 30 genes have been isolated from their critical intervals.3 Furthermore, a number of different mutations in several genes of the mitochondrial genome are responsible for syndromic and non-syndromic forms of hearing loss.4,5 Mutations responsible for maternally inherited non-syndromic hearing loss are so far confined to only two genes in the mitochondrial genome. These include mutations 7510T>C6 and 7511T>C7 in the tRNASer(UCN) gene, and 1095T>C8 and 1555A>G9 in the gene for the 12S rRNA. This last mutation is responsible for a dual phenotype, since it also confers increased susceptibility to the ototoxic action of aminoglycoside antibiotics.9 Most of these mutations have been reported in a small number of families from several countries, with the exception of 1555A>G, which seems to be more frequent than the others,10–13 although its real prevalence remains to be determined in most populations. Remarkably, in Spain it accounts for about 15–20% of all familial cases of non-syndromic hearing loss, irrespective of their mode of inheritance and age of onset14,15 (our unpublished results). In a majority of these patients, the hearing loss is not …

Validity of the Western Blot Immunoassay for Heat Shock Protein‐70 in Associated and Isolated Immunorelated Inner Ear Disease

Objective To assess the validity of the Western blot immunoassay for heat shock protein‐70 (hsp‐70) for diagnosis of autoimmune inner ear disease.

Sudden presentation of immune-mediated inner ear disease: characterization and acceptance of a cochleovestibular dysfunction

Since the McCabe report, growing indirect evidence has accumulated to indicate the implication of immune mechanisms in the pathogenesis of immune-mediated inner-ear disease (IMIED). A clinical study of a group of patients affected by this condition was performed in order to characterize the immune group, based on a recently reported profile, and compared with the vascular, viral and idiopathic aetiologies of sudden deafness. Patients affected by immune-mediated inner-ear disease had the best and the earliest recovery rate of hearing (p = 0.0028 and p = 0.017, respectively). However, this group of patients also had the higher rate of recurrence (p = 0.034), supporting the typical clinical course of the autoimmune disorders. On the basis of the results the criteria used in the diagnosis of the sudden presentation of the immune-mediated inner ear disease could be accepted leading to the characterization of this condition. Likewise, the role of the supporting cells in the pathogenesis of the IMIED is discussed.

Management of N 0 neck in laryngeal carcinoma. Impact on patient' s survival

Management of patients with carcinoma of the larynx should systematically include an appropriate treatment of lymph nodes according to the TNM stage. One of the most controversial points of the treatment in these patients is the management of the clinically negative neck (N(0)). A retrospective study of 295 patients with laryngeal carcinoma and N(0) neck undergoing treatment in our centre between 1983 and 1993 is presented. We observed a significant decrease in the survival of clinically N(0) patients with histologically affected lymph nodes. Lymphadenopathy was more frequently detected in patients with supraglottic tumours (38 per cent) when compared to glottic tumours (16 per cent). In our experience, routine bilateral and unilateral dissection of N(0) necks in all supraglottic tumours and in T3-T4 glottic tumours, respectively, is the most beneficial approach for patients in terms of survival.

Prevalencia de la mutación A1555G en el ADN mitocondrial en pacientes con patología auditiva o vestibular debida a la ototoxicidad de los aminoglucósidos

Resumen Objetivos Determinar la frecuencia de la mutacion A1555G del genoma mitocondrial en pacientes espanoles con ototoxicidad por aminoglucosidos Pacientes y metodos Se estudiaron 25 casos independientes, con un total de 39 individuos con patologia auditiva o vestibular causada por la ototoxicidad de los aminoglucosidos. De ellos, 18 pertenecian a 4 familias no relacionadas con historia de ototoxicidad por aminoglucosidos en mas de un miembro de la familia, 8 sujetos pertenecian a 8 familias en las que habia otros miembros con hipoacusia sin exposicion a aminoglucosidos, y 13 eran casos esporadicos. Entre los 13 casos esporadicos, habia 3 pacientes con afectacion vestibular, sin hipoacusia. Los 36 individuos restantes presentaban dano coclear. Se realizo la deteccion de la mutacion A1555G mediante tecnicas de diagnostico molecular Resultados se identifico la mutacion A1555G en todos los individuos de las 4 familias con dano auditivo por aminoglucosidos y en 6 de los 8 individuos con historia familiar de hipoacusia. Ninguno de los casos esporadicos portaba la mutacion Conclusiones una alta proporcion de los pacientes con dano auditivo debido a la ototoxicidad de los aminoglucosidos y que tienen antecedentes familiares de hipoacusia (relacionada o no con ototoxicidad) portan la mutacion A1555G

Inner Ear Malformations: Mondini’s Dysplasia

Advances in imaging techniques are enabling the detection of increasing numbers of inner ear malformations. Mondini’s dysplasia, whether alone or in association with other malformations, is one of those most frequently encountered. We report 4 cases of Mondini’s dysplasia treated by us, discussing recent embryological and genetic findings.

Small-cell neuroendocrine carcinoma of the nasal septum: unusual location for a known type of neoplasm

Abstract Small-cell neuroendocrine carcinoma (SNEC) is a distinct tumoral entity characterized by rapid local invasion, widespread dissemination and a poor prognosis. Due to its late discovery, localization is rarely precise. We report a case of a 39-year-old man whose clinical symptoms, radiological findings histological diagnosis and immunohistochemical staining confirm a primary SNEC of the nasal septum. Clinical features of nasal SNEC are nonspecific, including those resembling benign lesions; hence, it is likely to result in a delay in its discovery and treatment. Distinction between SNEC and other neuroendocrine tumors is also of great importance because of its prognostic implication, being SNEC the most aggressive in this group. Surgery, radiotherapy and chemotherapy alone or in combination have been used for these patients. Unfortunately, due to the rarity of this neoplasm, there is no specific recommendation on management guidelines, and treatment possibilities should be individualized for each patient.