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1.
Am J Case Rep ; 25: e944198, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850017

RESUMO

BACKGROUND H syndrome is an autosomal recessive disorder of histiocytic proliferation with clinical spectrum of unique cutaneous and systemic manifestations. There is no consistent treatment for the disease, and all available options are based on case reports. Here, we present the chronological progression of a case of H syndrome with typical cutaneous manifestations that was misdiagnosed early as meningitis-induced sensorineural hearing loss and later as a non-defined autoimmune connective tissue disease. A new tried, although failed, treatment option is described as well. CASE REPORT A 31-year-old Saudi woman born of a consanguineous marriage presented to our dermatology clinic with symmetrical indurated hyperpigmented to violaceous plaques over the medial thighs, upper legs, lower back, volar wrists, and upper arms, associated with hypertrichosis. Hallux valgus of the big toes was clinically detected as well. She had a history of sensorineural deafness, diabetes mellitus, chronic anemia, and hypothyroidism. Genetic analysis of the patient showed a homozygous frameshift pathogenic variant of the SLC29A3 gene, c.243del p.(Lys81Asnfs*20). Systemic treatments in the form of methotrexate and imatinib had been tried; however, both failed to control her sclerotic cutaneous changes. CONCLUSIONS Knowing the early life presentation and the variable clinical symptoms of H syndrome is crucial in early intervention and further prevention of the non-reversible changes. Moreover, avoiding unnecessary immunosuppressive medication use is warranted in certain circumstances.


Assuntos
Perda Auditiva Neurossensorial , Humanos , Feminino , Adulto , Perda Auditiva Neurossensorial/etiologia , Progressão da Doença , Histiocitose , Proteínas de Transporte de Nucleosídeos/genética , Falha de Tratamento , Contratura
2.
Codas ; 36(3): e20230094, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38896743

RESUMO

PURPOSE: To verify the influence of verbal intellectual-cognitive skills on speech perception in noise, in elderly with sensorineural hearing loss, considering education, age, and degree of hearing loss. METHODS: 36 elderly between 60 and 89 years old with bilateral sensorineural hearing loss participated in the study. After psychological assessment using the Wechsler Intelligence Scale for Adults (WAIS-III), they were grouped into (GI) 24 elderly without cognitive alteration and (GII) 12 elderly with risk of cognitive alteration. They underwent otorhinolaryngological assessment, audiological interview, pure tone audiometry, and assessment of speech perception in noise using the Hearing in Noise Test (HINT-Brazil). The Mann-Whitney U statistical test compared the results between the groups, and the Spearman correlation verified the variable's age, degree of hearing loss, and level of education. RESULTS: There was no difference between the groups in the ability to perceive speech in noise, except in the noise on the left condition, in which GII showed better performance in HINT-Brazil. The degree of hearing loss and level of education influenced the perception of speech in noise. The level of education was correlated with the WAIS-III results. CONCLUSION: The decline in verbal intellectual-cognitive skills did not affect speech perception of noise in the elderly with hearing loss. The degree of hearing loss and level of education influenced the performance of the elderly in the speech perception test in noise. Performance in verbal cognitive skills varied according to the level of education.


OBJETIVO: Verificar a influência das habilidades intelectuais-cognitivas verbais na percepção de fala no ruído, em idosos com perda auditiva sensorioneural, considerando a escolaridade, a idade e o grau da perda auditiva. MÉTODO: Participaram 36 idosos entre 60 e 89 anos com perda auditiva sensorioneural bilateral, que após avaliação psicológica por meio do Wechsler Intelligence Scale for Adults (WAIS III), foram divididos em (GI) 24 idosos sem alteração cognitiva e (GII) 12 idosos com risco de alteração cognitiva. Foram submetidos à avaliação otorrinolaringológica, entrevista audiológica, audiometria tonal liminar e a avaliação da percepção de fala no ruído por meio do Hearing in Noise Test (HINT-Brasil). O teste estatístico U de Mann-Whitney comparou os resultados entre os grupos, e a correlação de Spearman verificou as variáveis idade, grau da perda auditiva e nível de escolaridade. RESULTADOS: Não houve diferença entre os grupos na habilidade de percepção de fala no ruído, exceto na condição ruído à esquerda, no qual o GII apresentou melhor desempenho no HINT-Brasil. O grau da perda auditiva e o nível de escolaridade influenciaram na percepção de fala no ruído. O nível de escolaridade teve correlação com os resultados do WAIS III. CONCLUSÃO: O declínio das habilidades intelectuais-cognitivas verbais não interferiu na percepção de fala no ruído nos idosos com perda auditiva. O grau da perda auditiva e o nível de escolaridade influenciaram no desempenho dos idosos no teste de percepção de fala no ruído. O desempenho nas habilidades cognitivas verbais variou com o nível de escolaridade.


Assuntos
Perda Auditiva Neurossensorial , Ruído , Percepção da Fala , Humanos , Percepção da Fala/fisiologia , Idoso , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Perda Auditiva Neurossensorial/fisiopatologia , Audiometria de Tons Puros , Disfunção Cognitiva/fisiopatologia , Escolaridade
3.
Otol Neurotol ; 45(6): e468-e471, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38865723

RESUMO

OBJECTIVE: To report a fatal case of Susac syndrome in a congenitally deaf patient with a cochlear implant and a history of migraines, emphasizing the diagnostic challenges in patients with preexisting conditions. PATIENT: A 33-year-old male with congenital hearing loss, a cochlear implant, and chronic migraines who presented with mild subacute auditory disturbance and headaches that later progressed to severe encephalopathy. INTERVENTION: Explantation of a non-magnetic resonance imaging (MRI) compatible cochlear implant followed by MRI, fundoscopy, and the administration of immunosuppressive medications. MAIN OUTCOME MEASURES: Diagnosis was confirmed by characteristic MRI appearance and the presence of a hemi-retinal artery occlusion. RESULTS: After weeks of immunosuppressive treatment, the patient died of a global cerebral ischemic event of unknown origin. CONCLUSIONS: For patients with preexisting sensorineural hearing loss and cochlear implants, Susac syndrome poses a diagnostic challenge. Auditory disturbances in the absence of cochlear implant failure should prompt further evaluation for visual disturbances and encephalopathy. MRI and fundoscopy should be performed to detect other features of the disease.


Assuntos
Implantes Cocleares , Síndrome de Susac , Humanos , Masculino , Adulto , Síndrome de Susac/complicações , Síndrome de Susac/diagnóstico por imagem , Evolução Fatal , Imageamento por Ressonância Magnética , Surdez , Perda Auditiva Neurossensorial/etiologia , Implante Coclear , Transtornos de Enxaqueca/complicações , Oclusão da Artéria Retiniana/etiologia
4.
Sci Prog ; 107(2): 368504241262195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872447

RESUMO

A vestibular schwannoma is a benign tumor; however, the schwannoma itself and interventions can cause sensorineural hearing loss. Most vestibular schwannomas are unilateral tumors that affect hearing only on one side. Attention has focused on improving the quality of life for patients with unilateral hearing loss and therapeutic interventions to address this issue have been emphasized. Herein, we encountered a patient who was a candidate for hearing preservation surgery based on preoperative findings and had nonserviceable hearing after the surgery, according to the Gardner-Robertson classification. Postoperatively, the patient had decreased listening comprehension and ability to localize sound sources. He was fitted with bilateral hearing aids, and his ability to localize sound sources improved. Although the patient had postoperative nonserviceable hearing on the affected side and age-related hearing loss on the unaffected side, hearing aids in both ears were useful for his daily life. Therefore, the patient was able to maintain a binaural hearing effect and the ability to localize the sound source improved. This report emphasizes the importance of hearing preservation with vestibular schwannomas, and the demand for hearing loss rehabilitation as a postoperative complication can increase, even if hearing loss is nonserviceable.


Assuntos
Auxiliares de Audição , Neuroma Acústico , Humanos , Neuroma Acústico/cirurgia , Masculino , Pessoa de Meia-Idade , Perda Auditiva Neurossensorial/cirurgia , Perda Auditiva Neurossensorial/reabilitação , Perda Auditiva Neurossensorial/etiologia , Qualidade de Vida , Perda Auditiva/etiologia , Perda Auditiva/cirurgia , Perda Auditiva/reabilitação , Complicações Pós-Operatórias/etiologia
5.
Cir Cir ; 92(3): 324-330, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38862104

RESUMO

OBJECTIVE: The objective of the study is to compare the optic coherence tomography (OCT) parameters of the healthy and affected sides of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and to investigate the relationships between these and the improvement in hearing levels. METHODS: A bilateral eye evaluation of patients diagnosed with ISSNHL was performed with OCT. The ganglion cell complex (GCC) and retina nerve fiber layer (RNFL) thickness values were recorded and the differences between the two eyes were examined. RESULTS: An evaluation was made of 39 patients with a mean age of 44.82 ± 14.90 years. The RNFL thickness of the eyes was determined to be mean 89.87 ± 3.65 µm on the affected side and 103.87 ± 3.98 µm on the healthy control side (p = 0.0001). The mean GCC was determined to be mean 90.46 ± 3.49 µm on the affected side and 103.77 ± 3.96 µm on the healthy control side (p = 0.0001). CONCLUSIONS: A statistically significant difference was observed between the healthy and affected eyes of patients with ISSNHL with respect to mean GCC and mean RNFL thickness. OCT could be a useful technique for measuring this neural degeneration.


OBJETIVO: Comparar e investigar los parámetros de la tomografía de coherencia óptica (OCT) de los lados sanos y afectados de pacientes con pérdida auditiva neurosensorial súbita idiopática (PANSI). MÉTODO: La evaluación ocular bilateral de los pacientes diagnosticados con PANSI se realizó con OCT. Se registraron los valores de espesor del complejo de células ganglionares (CCG) y de la capa de fibras nerviosas de la retina (CFNR), y se examinaron las diferencias entre los dos ojos. RESULTADOS: Se evaluaron 39 pacientes, con una edad media de 44.82 ± 14.90 años. Se determinó que el grosor de la CFNR de los ojos era una media de 89.87 ± 3.65 µm en el lado afectado y 103.87 ± 3.98 µm en el lado de control sano (p = 0.0001). Se determinó que el CCG medio era 90.46 ± 3.49 µm en el lado afectado y 103.77 ± 3.96 µm en el lado de control sano (p = 0.0001). CONCLUSIONES: Se encontró una diferencia estadísticamente significativa entre los ojos sanos y afectados de pacientes con PANSI con respecto al CCG medio y al espesor medio de la CFNR. La OCT podría ser una técnica útil para medir esta degeneración neuronal.


Assuntos
Axônios , Fibras Nervosas , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Adulto , Feminino , Masculino , Fibras Nervosas/patologia , Pessoa de Meia-Idade , Axônios/patologia , Células Ganglionares da Retina/patologia , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Súbita/diagnóstico por imagem , Adulto Jovem
6.
Growth Horm IGF Res ; 76: 101594, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833815

RESUMO

OBJECTIVES: This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone. METHODS: Thirty acromegaly patients and 38 volunteers were included in the study. Pure tone average scores and middle ear RF values of the groups that underwent pure tone audiometry, tympanometry, and multifrequency tympanometry tests were compared. RESULTS: The pure tone mean was 14.95 ± 12.13 in acromegaly patients and 5.70 ± 8.52 in the control group (p:0.18). Sensorineural hearing loss(SNHL) was observed in 16.6% of the patients. The average middle ear RF was calculated as 815 ± 179.05 Hz in patients with acromegaly and 773 ± 127.15 in the control group. (p = 0.0001). CONCLUSION: This study is the first to evaluate middle-ear RF in acromegaly patients. Acromegaly-induced changes in soft tissues and bone structures impact middle ear functions. In this patient group, we found an increase in middle ear RF without conductive-type hearing loss and a 16.6% rate of SNHL.


Assuntos
Acromegalia , Orelha Média , Crânio , Humanos , Acromegalia/fisiopatologia , Acromegalia/patologia , Feminino , Orelha Média/patologia , Masculino , Adulto , Crânio/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos de Casos e Controles , Perda Auditiva Neurossensorial , Testes de Impedância Acústica , Audiometria de Tons Puros , Prognóstico
7.
BMC Med Genomics ; 17(1): 155, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840095

RESUMO

BACKGROUND: Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. METHODS: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. RESULTS: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21-47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32-26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05). CONCLUSION: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.


Assuntos
Mutação , RNA Ribossômico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , DNA Mitocondrial/genética , Predisposição Genética para Doença , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Estudos Retrospectivos , Fatores de Risco , RNA Ribossômico/genética , Taiwan/epidemiologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Peptídeos/genética , Peptídeos/metabolismo
8.
Noise Health ; 26(121): 205-213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904824

RESUMO

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) during pregnancy is a rare condition and has not been much studied. The study aimed to perform a systematic review and meta-analysis of the risk factors, complications, and treatment modalities for SSNHL in pregnant women. MATERIALS AND METHODS: PubMed, Web of Science, Scopus, ProQuest, and Google Scholar were used for the literature search. The Cochrane technique for assessing risk of bias was used for the article quality appraisal, and RevMan 5.4 was used for conducting the meta-analysis. Standard mean difference (SMD) and odds ratios with a 95% confidence interval (95% CI) were utilized. Heterogeneity and publication bias were assessed using the I-square (I2) test statistic and the Egger's test, respectively. RESULTS AND DISCUSSION: The seven primary studies employed prospective and retrospective study designs. The meta-analysis showed that there were fewer risk variables for SSNHL in the experimental group compared with those in the control group (SMD = -0.45 to 3.24, 95% CI = -3.063.63 to 2.16-2.85), indicating that the analysis revealed an insignificant difference. However, the treated patients presented hearing improvement, suggesting a significant analysis (SMD = -0.6710.20, 95% CI = -1.2713.51 to -0.066.88). Furthermore, after therapy, substantial differences were observed in SMD between the two groups (SMD = -0.7415.18, 95% CI = -1.2423.85 to -0.256.40) in favor of the experimental group patients, based on the analysis results of four included studies. However, the I2-value of 0% showed that the heterogeneity was low. CONCLUSION: SSNHL during pregnancy is a notably rare condition with an unknown cause. However, hormonal fluctuations, particularly increased levels of estrogen and progesterone during pregnancy, have been frequently implicated as potential triggers for SSNHL.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Complicações na Gravidez , Humanos , Gravidez , Feminino , Perda Auditiva Neurossensorial/etiologia , Fatores de Risco , Perda Auditiva Súbita/terapia , Perda Auditiva Súbita/etiologia , Complicações na Gravidez/terapia
9.
Noise Health ; 26(121): 220-225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904826

RESUMO

AIMS: Digital noise reduction (DNR) minimizes the effect of noise on speech signals by continuously monitoring frequency bands in the presence of noise. In the present study, we explored the effect of DNR technology on speech intelligibility in individuals using hearing aids (HAs) and investigated implications for daily use. METHODS AND MATERIAL: Eighteen participants with bilateral moderate sensorineural hearing loss (aged 16-45 years) were included. Bilateral receiver-in-the-ear HAs were fitted in the participants. The adaptive and nonadaptive (with a signal-to-noise ratio (SNR) of +5 and -5 dB, respectively) Turkish matrix sentence test (TURMatrix) in noise and free-field hearing assessments, including hearing thresholds with hearing aids, speech recognition thresholds (SRT), and speech discrimination scores, were conducted in two different conditions: HA in the DNR-on and DNR-off conditions. RESULTS: No significant difference was observed between free-field hearing assessments with the HA in the DNR-off and DNR-on conditions (P > 0.05). Furthermore, the adaptive and nonadaptive TURMatrix revealed significant differences between the scores under the DNR-on and DNR-off conditions (P < 0.05). Nevertheless, under the DNR-on condition, there was no correlation between free-field hearing assessments with HA and TURMatrix results (P > 0.05). However, a significant correlation was observed between SRT scores with HA and TURMatrix scores (adaptive and nonadaptive, +5 and -5 dB SNR, respectively) under the DNR-off condition (P < 0.05). CONCLUSION: Our study findings suggest that DNR can improve speech intelligibility in noisy environments. Therefore, DNR can enhance an individual's auditory comfort by improving their capacity to grasp speech in background noise.


Assuntos
Auxiliares de Audição , Perda Auditiva Neurossensorial , Ruído , Inteligibilidade da Fala , Humanos , Adulto , Masculino , Pessoa de Meia-Idade , Perda Auditiva Neurossensorial/reabilitação , Feminino , Adulto Jovem , Adolescente , Razão Sinal-Ruído , Limiar Auditivo , Percepção da Fala , Teste do Limiar de Recepção da Fala
10.
Sci Rep ; 14(1): 14203, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902305

RESUMO

Hearing problems are commonly diagnosed with the use of tonal audiometry, which measures a patient's hearing threshold in both air and bone conduction at various frequencies. Results of audiometry tests, usually represented graphically in the form of an audiogram, need to be interpreted by a professional audiologist in order to determine the exact type of hearing loss and administer proper treatment. However, the small number of professionals in the field can severely delay proper diagnosis. The presented work proposes a neural network solution for classification of tonal audiometry data. The solution, based on the Bidirectional Long Short-Term Memory architecture, has been devised and evaluated for classifying audiometry results into four classes, representing normal hearing, conductive hearing loss, mixed hearing loss, and sensorineural hearing loss. The network was trained using 15,046 test results analysed and categorised by professional audiologists. The proposed model achieves 99.33% classification accuracy on datasets outside of training. In clinical application, the model allows general practitioners to independently classify tonal audiometry results for patient referral. In addition, the proposed solution provides audiologists and otolaryngologists with access to an AI decision support system that has the potential to reduce their burden, improve diagnostic accuracy, and minimise human error.


Assuntos
Audiometria de Tons Puros , Redes Neurais de Computação , Humanos , Audiometria de Tons Puros/métodos , Feminino , Masculino , Perda Auditiva/diagnóstico , Perda Auditiva/classificação , Adulto , Pessoa de Meia-Idade , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/classificação , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/classificação
11.
Otolaryngol Pol ; 78(3): 1-6, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38808642

RESUMO

<b><br>Introduction:</b> Idiopathic sensorineural hearing loss of 30 decibels (dB) or more over at least three contiguous audiometric frequencies with an onset of less than 3 days is referred to as sudden sensorineural hearing loss (ISSNHL) and is known as an ENT (ear, nose, and throat) emergency. When a patient's hearing suddenly deteriorates, they become confused, anxious, and worried. One of the primary therapies for sudden sensorineural hearing loss is intratympanic steroids. Intratympanic injections of platelet-rich plasma (PRP) improve inner ear hair cells, which enhances hearing.</br> <b><br>Aim:</b> To show the safety and efficacy of intratympanic PRP injection in the management of ISSNHL in comparison with intratympanic steroid injection.</br> <b><br>Methods:</b> The study group was comprised of 100 patients who had experienced ISSNHL within 30 days with no retrocochlear pathology, as demonstrated by a negative MRI scan. 50 patients received 6 intratympanic steroid injections, while the remaining 50 patients received 2 intratympanic injections of PRP at a 1-week interval.</br> <b><br>Results:</b> A total of 39 patients with PRP injection noted an improvement in their hearing of 25 db after 2 weeks and of 30 db after 2 months, with improved speech discrimination of 26% after 2 weeks and of 28% after 2 months. 31 patients with intratympanic steroid injection noted an improvement in their hearing of 18 db after 2 weeks and of 22 db after 2 months, with improved speech discrimination of 21% after 2 weeks and of 24% after 2 months.</br> <b><br>Conclusions:</b> PRP appears safe and efficient for the treatment of ISSNHL, with a low cost and no systemic side effects, as with oral steroids. Therefore, such research should be continued.</br>.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Injeção Intratimpânica , Plasma Rico em Plaquetas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Perda Auditiva Neurossensorial/tratamento farmacológico , Estudos Transversais , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/terapia , Resultado do Tratamento , Idoso
12.
Genes (Basel) ; 15(5)2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38790200

RESUMO

Hearing loss (HL) is a common and multi-complex etiological deficit that can occur at any age and can be caused by genetic variants, aging, toxic drugs, noise, injury, viral infection, and other factors. Recently, a high incidence of genetic etiologies in congenital HL has been reported, and the usefulness of genetic testing has been widely accepted in congenital-onset or early-onset HL. In contrast, there have been few comprehensive reports on the relationship between late-onset HL and genetic causes. In this study, we performed next-generation sequencing analysis for 91 HL patients mainly consisting of late-onset HL patients. As a result, we identified 23 possibly disease-causing variants from 29 probands, affording a diagnostic rate for this study of 31.9%. The highest diagnostic rate was observed in the congenital/early-onset group (42.9%), followed by the juvenile/young adult-onset group (31.7%), and the middle-aged/aged-onset group (21.4%). The diagnostic ratio decreased with age; however, genetic etiologies were involved to a considerable degree even in late-onset HL. In particular, the responsible gene variants were found in 19 (55.9%) of 34 patients with a familial history and progressive HL. Therefore, this phenotype is considered to be a good candidate for genetic evaluation based on this diagnostic panel.


Assuntos
Idade de Início , Testes Genéticos , Perda Auditiva Neurossensorial , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Feminino , Masculino , Perda Auditiva Neurossensorial/genética , Adulto , Pessoa de Meia-Idade , Testes Genéticos/métodos , Adolescente , Idoso , Criança , Adulto Jovem , Pré-Escolar , Mutação , Predisposição Genética para Doença
13.
FASEB J ; 38(10): e23651, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38752537

RESUMO

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.


Assuntos
Autofagia , Interferon beta , Pressão Intraocular , Malha Trabecular , Autofagia/efeitos dos fármacos , Malha Trabecular/metabolismo , Malha Trabecular/efeitos dos fármacos , Humanos , Animais , Camundongos , Pressão Intraocular/fisiologia , Interferon beta/metabolismo , Masculino , Feminino , Glaucoma/patologia , Glaucoma/metabolismo , Glaucoma/genética , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Perda Auditiva Neurossensorial/metabolismo , Proteína DEAD-box 58/metabolismo , Proteína DEAD-box 58/genética , Camundongos Endogâmicos C57BL , Mutação , Atrofia Óptica/genética , Atrofia Óptica/metabolismo , Atrofia Óptica/patologia , Linhagem , Odontodisplasia , Calcificação Vascular , Hipoplasia do Esmalte Dentário , Metacarpo/anormalidades , Osteoporose , Doenças Musculares , Doenças da Aorta , Receptores Imunológicos
14.
Comput Biol Med ; 176: 108597, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763069

RESUMO

BACKGROUND: Recessive GJB2 variants, the most common genetic cause of hearing loss, may contribute to progressive sensorineural hearing loss (SNHL). The aim of this study is to build a realistic predictive model for GJB2-related SNHL using machine learning to enable personalized medical planning for timely intervention. METHOD: Patients with SNHL with confirmed biallelic GJB2 variants in a nationwide cohort between 2005 and 2022 were included. Different data preprocessing protocols and computational algorithms were combined to construct a prediction model. We randomly divided the dataset into training, validation, and test sets at a ratio of 72:8:20, and repeated this process ten times to obtain an average result. The performance of the models was evaluated using the mean absolute error (MAE), which refers to the discrepancy between the predicted and actual hearing thresholds. RESULTS: We enrolled 449 patients with 2184 audiograms available for deep learning analysis. SNHL progression was identified in all models and was independent of age, sex, and genotype. The average hearing progression rate was 0.61 dB HL per year. The best MAE for linear regression, multilayer perceptron, long short-term memory, and attention model were 4.42, 4.38, 4.34, and 4.76 dB HL, respectively. The long short-term memory model performed best with an average MAE of 4.34 dB HL and acceptable accuracy for up to 4 years. CONCLUSIONS: We have developed a prognostic model that uses machine learning to approximate realistic hearing progression in GJB2-related SNHL, allowing for the design of individualized medical plans, such as recommending the optimal follow-up interval for this population.


Assuntos
Conexina 26 , Perda Auditiva Neurossensorial , Aprendizado de Máquina , Humanos , Conexina 26/genética , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/fisiopatologia , Feminino , Masculino , Adulto , Criança , Adolescente , Pessoa de Meia-Idade , Pré-Escolar
15.
Proc Natl Acad Sci U S A ; 121(22): e2318859121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38771880

RESUMO

Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157, 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori et al., J. Am. Soc. Nephrol. 28, 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic et al., Proc. Natl. Acad. Sci. U.S.A. 93, 4229-4234 (1996)], and other illnesses.


Assuntos
Microscopia Crioeletrônica , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Animais , Humanos , Ratos , Ligantes , Endocitose , Agenesia do Corpo Caloso/metabolismo , Agenesia do Corpo Caloso/genética , Erros Inatos do Transporte Tubular Renal , Miopia , Hérnias Diafragmáticas Congênitas , Proteinúria , Perda Auditiva Neurossensorial
17.
J Med Case Rep ; 18(1): 241, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38734626

RESUMO

BACKGROUND: Mutations in the GJB2 gene, which encodes the protein connexin 26 and is involved in inner ear homeostasis, are identified in approximately 50% of patients with autosomal recessive nonsyndromic hearing loss, making it one of the primary causes of prelingual nonsyndromic hearing loss in various populations. The 35delG mutation, one of the most common mutations of the GJB2 gene, usually causes prelingual, bilateral mild to profound, nonprogressive sensorineural hearing loss. CASE PRESENTATION: We present an unusual case of an 18-year-old Turkish female with heterozygous 35delG mutation and postlingual, profound-sloping, progressive and fluctuating unilateral sensorineural hearing loss. The phenotype is different from the usual findings. CONCLUSIONS: The 35delG mutation causing hearing loss may not always be reflected in the phenotype as expected and therefore may have different audiologic manifestations.


Assuntos
Conexina 26 , Conexinas , Perda Auditiva Neurossensorial , Fenótipo , Humanos , Feminino , Adolescente , Perda Auditiva Neurossensorial/genética , Conexina 26/genética , Conexinas/genética , Mutação
18.
J Pediatr Ophthalmol Strabismus ; 61(3): e23-e27, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38788144

RESUMO

A 6-month-old female infant with megalophthalmos was referred with the suspicion of congenital glaucoma. Refractive measurements obtained with handheld autorefractometry were -7.00 -2.00 × 90° in the right eye and -6.00 -2.00 × 100° in the left eye and ultrasonic axial lengths were 22.50 mm in both eyes. Intraocular pressures and vertical and horizontal corneal diameters of the proband were 11 mm Hg, 11 mm, and 11.50 mm in both eyes, respectively. She was diagnosed as having early-onset high myopia. Her father also had degenerative high myopia (-12.00 diopters) in the right eye, bilateral congenital lens opacities, and retinal detachment in the left eye. Her mother was emmetropic with normal eye examination results. Clinical exome sequencing analysis revealed a novel ENST00000380518.3 c.3528_3530 delins GACCATTAGCA (Chr12:48369813: GCA > TGCTAATGGTC) variant in the collagen type II alpha 1 chain (COL2A1) on chromosome 12q13 (OMIM 108300), consistent with the Stickler syndrome type 1. Subsequent segregation analysis revealed paternal inheritance. Although many pathogenic null variants have been described within the COL2A1 gene, there is currently no documented literature pertaining to this specific variant, making this the inaugural report of its manifestation in scientific discourse. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e23-e27.].


Assuntos
Artrite , Colágeno Tipo II , Doenças do Tecido Conjuntivo , Perda Auditiva Neurossensorial , Linhagem , Feminino , Humanos , Lactente , Artrite/genética , Artrite/diagnóstico , Colágeno Tipo II/genética , Doenças do Tecido Conjuntivo/genética , Doenças do Tecido Conjuntivo/diagnóstico , DNA/genética , Análise Mutacional de DNA , Sequenciamento do Exoma , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/diagnóstico , Pressão Intraocular/fisiologia , Mutação , Descolamento Retiniano/genética , Descolamento Retiniano/diagnóstico , Turquia
19.
PLoS One ; 19(5): e0302447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38713651

RESUMO

OBJECTIVE: Vascular disease like small-vessel disease (SVD) is the most likely cause among the potential causes of Sudden sensorineural hearing loss (SSNHL). Understanding the relationship between SVD and SSNHL is crucial for developing effective prevention and treatment strategies. To confirm the relationship between SVD and SSNHL, the effect of SVD is confirmed by focusing on the duration and recurrence of SSNHL. METHODS: This article reports a retrospective observational study that investigated the relationship between SVD and SSNHL using the South Korea Health Insurance Review and Assessment Service (HIRA) database from 2010 to 2020. This retrospective observational study included 319,569 SSNHL patients between 2010 and 2020. RESULTS: Participant demographics were controlled using Propensity Score Matching. The hazard ratios (HR) for the effect of SVD on the duration of SSNHL were 1.045 for the group with SVD before the onset of SSNHL and 1.234 for the group with SVD after the onset of SSNHL. SVD was statistically significant for the recurrence of SSNHL, with an odds ratio of 1.312 in the group with SVD compared to the group without SVD. The HR for the period until a recurrence in the group with SVD was 1.062. CONCLUSIONS: The study identified SVD as a possible cause of SSNHL and found that the duration of SSNHL increased only in the presence of SVD. SVD also affected the recurrence of SSNHL, with the recurrence rate being 1.312 times higher in the group with SVD.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Masculino , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/complicações , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , República da Coreia/epidemiologia , Perda Auditiva Súbita/etiologia , Perda Auditiva Súbita/epidemiologia , Adulto , Idoso , Fatores de Risco , Recidiva , Adulto Jovem , Pontuação de Propensão
20.
BMJ Case Rep ; 17(5)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740443

RESUMO

Alport syndrome and autosomal dominant polycystic kidney disease are monogenic causes of chronic kidney disease and end-stage kidney failure. We present a case of a man in his 60s with progressive chronic kidney disease, bilateral sensorineural hearing loss and multiple renal cysts. Genetic analysis revealed a heterozygous variant in COL4A3 (linked to Alport syndrome) and in the GANAB gene (associated with a milder form of autosomal dominant polycystic kidney disease). Although each variant confers a mild risk of developing end-stage kidney disease, the patient presented a pronounced and accelerated progression of chronic kidney disease, which goes beyond what would be predicted by adding up their individual effects. This suggests a potential synergic effect of both variants, which warrants further investigation.


Assuntos
Colágeno Tipo IV , Nefrite Hereditária , Rim Policístico Autossômico Dominante , Humanos , Nefrite Hereditária/genética , Nefrite Hereditária/complicações , Nefrite Hereditária/diagnóstico , Masculino , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/complicações , Colágeno Tipo IV/genética , Pessoa de Meia-Idade , Autoantígenos/genética , Progressão da Doença , Falência Renal Crônica/genética , Falência Renal Crônica/etiologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/diagnóstico
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