ABSTRACT
Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1ß into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 × 10-6) and IGLV3-21 (p = 6.28 × 10-3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1ß with up-regulation of IL6 (p = 7.65 × 10-8) and INHBA (p = 3.39 × 10-7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.
Subject(s)
Meniere Disease , Humans , Meniere Disease/metabolism , Leukocytes, Mononuclear/metabolism , Interleukin-6/metabolism , CD8-Positive T-Lymphocytes/metabolism , Gene Expression ProfilingABSTRACT
Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare missense single nucleotide variants in synaptic genes. Rare structural variants (SVs) may also contribute to MD and severe tinnitus. In this study, we analyzed exome sequencing data from 310 MD Spanish patients and selected 75 patients with severe tinnitus based on a Tinnitus Handicap Inventory (THI) score > 68. Three rare deletions were identified in two unrelated individuals overlapping the ERBB3 gene in the positions: NC_000012.12:g.56100028_56100172del, NC_000012.12:g.56100243_56101058del, and NC_000012.12:g.56101359_56101526del. Moreover, an ultra-rare large duplication was found covering the AP4M1, COPS6, MCM7, TAF6, MIR106B, MIR25, and MIR93 genes in another two patients in the NC_000007.14:g.100089053_100112257dup region. All the coding genes exhibited expression in brain and inner ear tissues. These results confirm the contribution of large SVs to severe tinnitus in MD and pinpoint new candidate genes to get a better molecular understanding of the disease.
Subject(s)
Ear, Inner , Meniere Disease , TATA-Binding Protein Associated Factors , Tinnitus , Humans , Meniere Disease/genetics , Tinnitus/genetics , Genes, Regulator , Genetic Variation , COP9 Signalosome Complex , Adaptor Proteins, Signal TransducingABSTRACT
Vestibular Migraine in children can mimic other disorders, especially at presentation. Outcome is hard to predict and management may be challenging due to the fact that many of the patients are too young to describe their symptoms and these are not always accompanied by headache. OBJECTIVE: To assess vestibulo-ocular reflex (VOR) in pediatric patients who meet criteria for defined Vestibular Migraine and to compare results to healthy controls. METHODS: Twenty-one patients aged 11-16 years were included in this prospective multicentric study. VOR was assessed using the video Head Impulse Test by EyeSeeCam®(Interacoustics, Denmark). RESULTS: Patients with Vestibular Migraine (VM) have higher values of gain compared to asymptomatic patients. CONCLUSION: Video Head Impulse Test (vHIT) is a useful and relatively fast-to-perform examination in children compared to other vestibular tests. Patients with VM seem to have higher values of gain at vHIT.
Subject(s)
Head Impulse Test , Migraine Disorders/diagnosis , Migraine Disorders/physiopathology , Reflex, Vestibulo-Ocular , Adolescent , Case-Control Studies , Child , Female , Head Impulse Test/methods , Humans , Male , Prospective StudiesABSTRACT
En este informe se describen dos casos de la variante letal del síndrome de Prune Belly en que la obstrucción de la uretra produjo graves alteraciones del sistema urinario con distensión vesical y ureteral con repercusión secundaria en la pared abdominal y daño renal bilateral por displasia. Se comenta la etiopatogenia de este síndrome de acuerdo a la teoría embriológica del mesodermo, así como de la teoría de la secuencia de la obstrucción uretral en las etapas tempranas del desarrollo que repercuten en la pared abdominal. En estos casos descritos, el grado de obstrucción del tracto urinario repercutió en el desarrollo de malformaciones letales
