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Primary ciliary dyskinesia (PCD) is a hereditary disease caused by genes related to motile cilia. We report two male pediatric cases of PCD caused by hemizygous pathogenic variants in the OFD1 centriole and centriolar satellite protein (OFD1) gene. The variants were NM_003611.3: c.[2789_2793delTAAAA] (p.[Ile930LysfsTer8]) in Case 1 and c.[2632_2635delGAAG] (p.[Glu878LysfsTer9]) in Case 2. Both cases had characteristic recurrent respiratory infections. Neither case had symptoms of oral-facial-digital syndrome type I. We identified a variant (c.2632_2635delGAAG) that has not been previously reported in any case of OFD1-PCD.
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OBJECTIVE: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients. METHODS: An ad hoc academic committee was organized under the Japanese Rhinologic Society to produce a practical guide, with participation by committee members from several academic societies in Japan. The practical guide including diagnostic criteria for PCD was approved by the Japanese Rhinologic Society, Japanese Society of Otolaryngology-Head and Neck Surgery, Japanese Respiratory Society, and Japanese Society of Pediatric Pulmonology. RESULTS: The diagnostic criteria for PCD consist of six clinical features, six laboratory findings, differential diagnosis, and genetic testing. The diagnosis of PCD is categorized as definite, probable, or possible PCD based on a combination of the four items above. Diagnosis of definite PCD requires exclusion of cystic fibrosis and primary immunodeficiency, at least one of the six clinical features, and a positive result for at least one of the following: (1) Class 1 defect on electron microscopy of cilia, (2) pathogenic or likely pathogenic variants in a PCD-related gene, or (3) impairment of ciliary motility that can be repaired by correcting the causative gene variants in iPS cells established from the patient's peripheral blood cells. CONCLUSION: This practical guide provides clinicians with useful information for the diagnosis and management of PCD in Japan.
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Pruebas Genéticas , Síndrome de Kartagener , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/terapia , Síndrome de Kartagener/genética , Diagnóstico Diferencial , Cilios/ultraestructura , Cilios/patología , Japón , Dineínas Axonemales/genética , ProteínasRESUMEN
BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.
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Asma Variante con Tos , Reflujo Gastroesofágico , Humanos , Tos Crónica , Japón/epidemiología , Prevalencia , Calidad de Vida , Tos/epidemiología , Tos/etiología , Tos/diagnóstico , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/epidemiología , Enfermedad CrónicaRESUMEN
We speculated that increased blood-plasma levels of Substance P may serve as an indicator of glottal incompetence, which is usually indicated by reduced maximum phonation time. We performed an initial study to test the plausibility of this hypothesis. Patients with dysphonia caused by glottal incompetence were asked to perform vocal exercises for six months to reduce glottal incompetence and we compared the plasma concentration of Substance P before and after the vocal exercise to detect correlation between maximum phonation time and plasma concentration of Substance P. Based on the results, we further hypothesized that patients exhibiting dysphonia with maximum phonation time less than 14 s, in particular less than 10 sec, caused by glottal incompetence may have increased plasma concentration of Substance P with the results of elevated thresholds of cough reflex associated with subclinical aspiration in airways. Further study is needed on patients with decreased Substance P levels, with low scores on Activities of Daily Living and who are hospitalized with aspiration pneumonia.
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OBJECTIVE: This study aimed to determine whether surface-based morphometry of preoperative whole-brain three-dimensional T1-weighted magnetic resonance imaging (MRI) images can predict the clinical outcomes of cochlear implantation. STUDY DESIGN: This was an observational, multicenter study using preoperative MRI data. SETTING: The study was conducted at tertiary care referral centers. PATIENTS: Sixty-four patients with severe to profound hearing loss (≥70 dB bilaterally), who were scheduled for cochlear implant (CI) surgery, were enrolled. The patients included 19 with congenital hearing loss and 45 with acquired hearing loss. INTERVENTIONS: Participants underwent CI surgery. Before surgery, high-resolution three-dimensional T1-weighted brain MRI was performed, and the images were analyzed using FreeSurfer. MAIN OUTCOME MEASURES: The primary outcome was monosyllable audibility under quiet conditions 6 months after surgery. Cortical thickness residuals within 34 regions of interest (ROIs) as per the Desikan-Killiany cortical atlas were calculated based on age and healthy-hearing control regression lines. RESULTS: Rank logistic regression analysis detected significant associations between CI effectiveness and five right hemisphere ROIs and five left hemisphere ROIs. Predictive modeling using the cortical thickness of the right entorhinal cortex and left medial orbitofrontal cortex revealed a significant correlation with speech discrimination ability. This correlation was higher in patients with acquired hearing loss than in those with congenital hearing loss. CONCLUSIONS: Preoperative surface-based morphometry could potentially predict CI outcomes and assist in patient selection and clinical decision making. However, further research with larger, more diverse samples is necessary to confirm these findings and determine their generalizability.
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Implantación Coclear , Implantes Cocleares , Sordera , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Percepción del Habla , Humanos , Implantación Coclear/métodos , Resultado del Tratamiento , Pérdida Auditiva/cirugía , Pérdida Auditiva Sensorineural/cirugía , Sordera/cirugíaRESUMEN
Primary ciliary dyskinesia (PCD) is a hereditary disease caused by pathogenic variants in genes associated with motile cilia. Some variants responsible for PCD are reported to be ethnic-specific or geographical-specific. To identify the responsible PCD variants of Japanese PCD patients, we performed next-generation sequencing of a panel of 32 PCD genes or whole-exome sequencing in 26 newly identified Japanese PCD families. We then combined their genetic data with those from 40 Japanese PCD families reported previously, for an overall analysis of 66 unrelated Japanese PCD families. We conducted Genome Aggregation Database and TogoVar database analyses to reveal the PCD genetic spectrum of the Japanese population and compare with other ethnic groups worldwide. We identified 22 unreported variants among the 31 patients in the 26 newly identified PCD families, including 17 deleterious variants estimated to cause lack of transcription or nonsense-mediated mRNA decay and 5 missense mutations. In all 76 PCD patients from the 66 Japanese families, we identified 53 variants on 141 alleles in total. Copy number variation in DRC1 is the most frequent variant in Japanese PCD patients, followed by DNAH5 c.9018C>T. We found 30 variants specific to the Japanese population, of which 22 are novel. Furthermore, 11 responsible variants in the Japanese PCD patients are common in East Asian populations, while some variants are more frequent in other ethnic groups. In conclusion, PCD is genetically heterogeneous between different ethnicities, and Japanese PCD patients have a characteristic genetic spectrum.
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Trastornos de la Motilidad Ciliar , Variaciones en el Número de Copia de ADN , Pueblos del Este de Asia , Humanos , Trastornos de la Motilidad Ciliar/genética , Trastornos de la Motilidad Ciliar/patología , Variaciones en el Número de Copia de ADN/genética , Genómica , MutaciónRESUMEN
BACKGROUND: Allergic rhinitis (AR) is the most common allergic disease in children. The development process of AR in early childhood, however, is not well understood. We prospectively investigated the process in regard to not only the nasal symptoms and sensitization but also the nasal cytology, in relation to recurrent wheeze in a high-risk cohort. METHODS: Infants under 2 years of age with atopic dermatitis (AD) and/or food allergy (FA) symptoms were recruited and followed prospectively for 2 years. The phenotype of perennial AR was classified based on the presence/absence of (1) persistent nasal symptoms, (2) nasal eosinophils, and (3) HDM sensitization, the most common allergen for perennial AR in Japan. AR-like phenotypes were defined as positive for at least two of those three categories. High-risk recurrent wheezer was diagnosed based on the Japanese guidelines and Global Initiative for Asthma. Cox proportional hazards regression analyses for high-risk recurrent wheeze and the AR-like phenotype, adjusting for known covariate risk factors for asthma. RESULTS: A total of 299 children were enrolled, and 237 subjects (78%) completed the 2-year observation. The prevalence of eosinophilia in nasal secretions increased from 18.5% to 69.9%, while HDM-specific IgE ≥ 0.35 kUA /L increased from 30.6% to 74.8%. AR-like phenotypes increased from 18.4% to 65.0%. The AR-like phenotype at 2 years was associated with development of high-risk recurrent wheezer (HR 2.062; 95% CI 1.005-4.796). CONCLUSIONS: The prevalence of an HDM-related AR-like phenotype was markedly increased during infancy in infants with AD/FA and was associated with high-risk recurrent wheezer.
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Rinitis Alérgica Perenne , Rinitis Alérgica , Alérgenos , Preescolar , Humanos , Inmunoglobulina E , Lactante , Estudios Prospectivos , Rinitis Alérgica Perenne/diagnósticoRESUMEN
Some patients have an atypical form of branchio-oto-renal (BOR) syndrome, which does not satisfy the diagnostic criteria, despite carrying a pathogenic variant (P variant) or a likely pathogenic variant (LP variant) of a causative gene. P/LP variants phenotypic indices have yet to be determined in patients with typical and atypical BOR syndrome. We hypothesized that determining phenotypic and genetic differences between patients with typical and atypical BOR syndrome could inform such indices. Subjects were selected from among patients who underwent genetic testing to identify the cause of hearing loss. Patients were considered atypical when they had two major BOR diagnostic criteria, or two major criteria and one minor criterion; 22 typical and 16 atypical patients from 35 families were included. Genetic analysis of EYA1, SIX1, and SIX5 was conducted by direct sequencing and multiplex ligation-dependent probe amplification. EYA1 P/LP variants were detected in 25% and 86% of atypical and typical patients, respectively. Four EYA1 P/LP variants were novel. Branchial anomaly, inner ear anomaly, and mixed hearing loss were correlated with P/LP variants. Development of refined diagnostic criteria and phenotypic indices for atypical BOR syndrome will assist in effective detection of patients with P/LP variants among those with suspected BOR syndrome.
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Síndrome Branquio Oto Renal/genética , Proteínas de Homeodominio/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Nucleares/genética , Fenotipo , Proteínas Tirosina Fosfatasas/genética , Femenino , Humanos , Masculino , LinajeRESUMEN
It remains unclear to what extent newborn hearing screening (NHS) detects congenital cytomegalovirus (cCMV)-associated sensorineural hearing loss (SNHL) in Japan. This study aimed to clarify the NHS results and audiological characteristics of patients with cCMV-associated SNHL. A total of 541 individuals with unilateral or bilateral hearing loss of unknown etiology were examined for cCMV infection. cCMV infection was defined by the presence of CMV DNA in the dried umbilical cord detected using real-time quantitative PCR. NHS results and audiological data were retrospectively obtained from medical records. Forty-four cases (8.1%) were positive for cCMV infection. Of them, 33 cases underwent NHS and 13 cases (39.4%) passed NHS bilaterally. The pure-tone audiograms of 21 patients were obtained. There were seven cases of unilateral SNHL, five cases of asymmetric bilateral SNHL, and nine cases of symmetric bilateral SNHL. cCMV-related hearing loss is highly heterogeneous, and there is a high risk of missing this condition through NHS.
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OBJECTIVE: This study assessed maternal cytomegalovirus antibodies, and the occurrence of primary and congenital cytomegalovirus infections, and risk factors of congenital infection after a maternal primary infection. STUDY DESIGN: We included 19,435 pregnant women in Japan, who were tested for serum cytomegalovirus antibodies before 20 gestational weeks. Immunoglobulin (Ig) G avidity was evaluated in women with both IgG and IgM antibodies; tests were repeated at ≥28 gestational weeks among women without IgG and IgM antibodies. RESULT: Primary and congenital infections were 162 and 23 cases, respectively. The risk ratios for congenital infection were 8.18 (95% confidence interval: 2.44-27.40) in teenage versus older women, and 2.25 (95% confidence interval: 1.28-3.94) in parity ≥ 2 versus parity ≤ 1. Of 22 live birth congenital infection cases, three had abnormal neurological findings. CONCLUSION: We demonstrated teenage and parity ≥ 2 pregnant women as risk factors of post-primary congenital infection.
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Infecciones por Citomegalovirus , Complicaciones Infecciosas del Embarazo , Adolescente , Anciano , Anticuerpos Antivirales , Citomegalovirus , Infecciones por Citomegalovirus/epidemiología , Femenino , Humanos , Inmunoglobulina M , Relaciones Madre-Hijo , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Estudios ProspectivosRESUMEN
OBJECTIVE: Variants in GJB2 can cause autosomal recessive deafness (DFNB1). There is evidence for genotype-phenotype correlations of GJB2 variants; however, several genotypes can cause varying levels of hearing loss likely attributable to differences in genetic or environmental background. As siblings share approximately 50% of their genetic background and usually have a common environmental background, analysis of phenotypes of siblings with a specific GJB2 variant may reveal factors relevant to phenotypic variation. There have been no previous analyses of differences in hearing among siblings carrying a single GJB2 genotype. Here, we investigated hearing differences between siblings with a single GJB2 variant, which can cause various levels of hearing loss. METHODS: We examined hearing levels in 16 pairs of siblings homozygous for the c.235delC variant of GJB2. Differences in hearing acuity between sibling pairs were detected by auditory evaluation. RESULTS: Average differences in acoustic threshold >30 dB were observed between five pairs of siblings, whereas the remaining 11 pairs had average threshold values within approximately 10 dB of one another. Hearing loss varied from moderate to profound. CONCLUSION: Our results indicate that auditory acuity associated with homozygosity for GJB2 c.235delC can vary in degree; however, in approximately 70% of younger siblings, it was approximately the same as that in the first child, despite a diverse spectrum of hearing loss among different families. These results suggest that differences in genetic background may modify the phenotype associated with homozygous GJB2 c.235delC.
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Sordera , Hermanos , Conexina 26/genética , Conexinas/genética , Audición , Humanos , MutaciónRESUMEN
We report the first Japanese case of primary ciliary dyskinesia caused by DNAH9 variations. The patient, a 5-year-old girl, had repeated episodes of productive cough after contracting the common cold at the age of 1 year and 6 months. She did not have a situs abnormality or congenital heart defect. We identified two novel DNAH9 variants, NM_001372.3: c. [1298C>G];[5547_5550delTGAC], (p.[Ser433Cys];[Asp1850fs]).
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OBJECTIVE: Hearing loss caused by GJB2 mutations is inherited in an autosomal recessive manner (DFNB1); thus siblings of an affected child have a 25% chance of also being affected. Hearing loss among subsequent siblings carrying the same GJB2 mutation is a concern for parents and a frequent topic of enquiry during genetic counseling. Evidence exists for genotype-phenotype correlations of GJB2 mutations; however, no analysis of differences in hearing among siblings, in whom the common genetic background may decrease variation, has been reported. The purpose of the present study was to investigate hearing differences between siblings with identical GJB2 mutations. METHODS: We examined the hearing levels of 12 pairs of siblings; each pair had the same pathogenic GJB2 mutations. Differences in hearing acuity between sibling pairs detected by auditory evaluation. RESULTS: No significant correlation was detected between the average hearing levels of first and second affected siblings. Average differences in acoustic threshold >30 dB were observed between four pairs of siblings, whereas the remaining eight pairs had average threshold values within 20 dB of one another. CONCLUSION: Our results indicate that auditory acuity would be expected to approximate that found in the first child in approximately 70% of subsequent children with GJB2-mediated hearing loss, whereas 30% of subsequent siblings would have average differences of >30 dB.
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Umbral Auditivo , Conexina 26/genética , Pérdida Auditiva/fisiopatología , Mutación , Hermanos , Audiometría , Niño , Preescolar , Sordera/genética , Sordera/fisiopatología , Femenino , Genotipo , Pérdida Auditiva/genética , Humanos , Lactante , MasculinoRESUMEN
Hereditary hearing loss is challenging to diagnose because of the heterogeneity of the causative genes. Further, some genes involved in hereditary hearing loss have yet to be identified. Using whole-exome analysis of three families with congenital, severe-to-profound hearing loss, we identified a missense variant of SLC12A2 in five affected members of one family showing a dominant inheritance mode, along with de novo splice-site and missense variants of SLC12A2 in two sporadic cases, as promising candidates associated with hearing loss. Furthermore, we detected another de novo missense variant of SLC12A2 in a sporadic case. SLC12A2 encodes Na+, K+, 2Cl- cotransporter (NKCC) 1 and plays critical roles in the homeostasis of K+-enriched endolymph. Slc12a2-deficient mice have congenital, profound deafness; however, no human variant of SLC12A2 has been reported as associated with hearing loss. All identified SLC12A2 variants mapped to exon 21 or its 3'-splice site. In vitro analysis indicated that the splice-site variant generates an exon 21-skipped SLC12A2 mRNA transcript expressed at much lower levels than the exon 21-included transcript in the cochlea, suggesting a tissue-specific role for the exon 21-encoded region in the carboy-terminal domain. In vitro functional analysis demonstrated that Cl- influx was significantly decreased in all SLC12A2 variants studied. Immunohistochemistry revealed that SLC12A2 is located on the plasma membrane of several types of cells in the cochlea, including the strial marginal cells, which are critical for endolymph homeostasis. Overall, this study suggests that variants affecting exon 21 of the SLC12A2 transcript are responsible for hereditary hearing loss in humans.
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Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Sensorineural/genética , Mutación , Dominios Proteicos/genética , Miembro 2 de la Familia de Transportadores de Soluto 12/química , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cloruros/metabolismo , Cóclea/metabolismo , Cóclea/patología , Sordera/congénito , Sordera/genética , Exones/genética , Femenino , Expresión Génica , Células HEK293 , Humanos , Lactante , Macaca fascicularis , Masculino , Linaje , Empalme del ARN , ARN Mensajero/análisis , ARN Mensajero/genética , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismoRESUMEN
OBJECTIVES: The aim of the study was to clarify differences in the prevalence and features of bony malformations in inner ear between congenital unilateral sensorineural hearing loss (USNHL) and congenital bilateral sensorineural hearing loss (BSNHL). METHODS: We conducted a retrospective study of 378 consecutive infants referred from routine newborn hearing screening in the past 18 years. Clinical background, audiological data, and temporal bone computed tomography (CT) findings were analyzed. The prevalence of malformations between USNHL and BSNHL groups were compared using the Chi-square test. RESULTS: The proportion of family history of hearing loss was significantly higher in infants with BSNHL than in those with USNHL (26/107 [24.3%] vs. 4/105 [3.7%]; pâ¯=â¯0.0001). Temporal bone CT scanning revealed significantly a higher prevalence of inner ear malformations in infants with USNHL than in those with BSNHL (93/109 [85.3%] vs. 4/107 [3.7%]; pâ¯<â¯0.0001). The most frequent anomaly in USNHL was cochlear nerve canal stenosis (69.7%), followed by cochlear malformations (20.2%), and narrow internal auditory canal (17.4%). Four infants with BSNHL accompanied by inner ear anomaly had complications such as Down's syndrome, developmental delay, or epilepsy. CONCLUSIONS: The prevalence of bony malformations in inner ear and/or IAC was markedly higher in infants with congenital USNHL than in infants with BSNHL. Temporal bone CT scanning may help to clarify the etiology of congenital hearing loss, especially in USNHL.
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Oído Interno/anomalías , Pérdida Auditiva Bilateral/congénito , Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Unilateral/congénito , Oído Interno/diagnóstico por imagen , Femenino , Predisposición Genética a la Enfermedad , Pérdida Auditiva Bilateral/genética , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Unilateral/genética , Humanos , Lactante , Recién Nacido , Masculino , Prevalencia , Estudios Retrospectivos , Hueso Temporal/anomalías , Hueso Temporal/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions. The purpose of this study was to investigate the time course of changes in distortion product otoacoustic emissions (DPOAEs) in association with patients' genetic and clinical backgrounds, including the use of hearing aids. DESIGN: DPOAE measurements from 31 patients with AN were assessed. Genetic analyses for GJB2, OTOF, and mitochondrial m.1555A> G and m.3243A> G mutations were conducted for all cases, and the analyses for CDH23 and OPA1 were conducted for the selected cases. Patients who were younger than 10 years of age at the time of AN diagnosis were designated as the pediatric AN group (22 cases), and those who were 18 years of age or older were designated as the adult AN group (9 cases). DPOAE was measured at least twice in all patients. The response rate for DPOAEs was defined and analyzed. RESULTS: The pediatric AN group comprised 10 patients with OTOF mutations, 1 with GJB2 mutations, 1 with OPA1 mutation, and 10 with indefinite causes. Twelve ears (27%) showed no change in DPOAE, 20 ears (46%) showed a decrease in DPOAE, and 12 ears (27%) lost DPOAE. Loss of DPOAE occurred in one ear (2%) at 0 years of age and four ears (9%) at 1 year of age. The time courses of DPOAEs in patients with OTOF mutations were divided into those with early loss and those with no change, indicating that the mechanism for deterioration of DPOAEs includes not only the OTOF mutations but also other common modifier factors. Most, but not all, AN patients who used hearing aids showed deterioration of DPOAEs after the start of using hearing aids. A few AN patients also showed deterioration of DPOAEs before using hearing aids. The adult AN group comprised 2 patients with OPA1 mutations, 2 with OTOF mutations, and 5 with indefinite causes. Four ears (22%) showed no change in DPOAE, 13 ears (72%) showed a decrease, and one ear (6%) showed a loss of DPOAE. Although the ratio of DPOAE decrease was higher in the adult AN group than in the pediatric AN group, the ratio of DPOAE loss was lower in the adult AN group. DPOAE was not lost in all four ears with OPA1 mutations and in all four ears with OTOF mutations in the adult group. CONCLUSIONS: DPOAE was decreased or lost in approximately 70% of pediatric and about 80% of adult AN patients. Eleven percent of pediatric AN patients lost DPOAEs by 1 year of age. Genetic factors were thought to have influenced the time course of DPOAEs in the pediatric AN group. In most adult AN patients, DPOAE was rarely lost regardless of the genetic cause.
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Pérdida Auditiva Central/fisiopatología , Emisiones Otoacústicas Espontáneas/fisiología , Adolescente , Adulto , Anciano , Proteínas Relacionadas con las Cadherinas , Cadherinas/genética , Niño , Preescolar , Conexina 26 , Conexinas/genética , Errores Diagnósticos , Progresión de la Enfermedad , Femenino , GTP Fosfohidrolasas/genética , Genes Mitocondriales/genética , Pérdida Auditiva Central/diagnóstico , Pérdida Auditiva Central/genética , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Genetic and environmental factors are proposed to be involved in cedar pollen allergy sensitization and onset. The impact of these factors will provide key information for the prevention of cedar pollen sensitization and allergy onset, which we investigated in this cross-sectional study. METHODS: Subjects were 382 young adult volunteers who completed a self-administered questionnaire on self-reported subjective symptoms of pollinosis, physician-diagnosed pollinosis, and background factors. We also measured their serum IgE antibody titers specific for cedar, cypress, and mites. Factors associated with subjective symptoms, physician diagnosis, and the three specific antigens were determined using both univariate and multivariate analyses. RESULTS: Sensitization to cedar, cypress, and mites, defined as specific IgE levels of class 1 or above, was found in 78.8%, 64.4%, and 56.0% of subjects, respectively. The prevalence of cedar pollinosis was 41.2% based on subjective symptoms and 22.2% based on physician diagnosis. Factors associated with increased cedar pollen sensitization were mite sensitization, comorbid allergic rhinitis, and family history of cedar pollinosis. Risk-reducing factors for cedar pollen sensitization were keeping a cat, number of common colds, and hours of sleep. Risk-increasing factors for both subjective pollinosis symptoms and physician-diagnosed pollinosis were comorbid allergic rhinitis and family history of cedar pollinosis. CONCLUSIONS: Sensitization to cedar pollen in this population was extremely high. Both common and distinct factors were associated with sensitization to pollen and with the development of pollinosis. The distinct factors were associated with sensitization to cedar and cypress antigens.
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Alérgenos/inmunología , Cryptomeria/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Pueblo Asiatico , Niño , Preescolar , Cupressus/inmunología , Dermatophagoides pteronyssinus/inmunología , Femenino , Humanos , Inmunoglobulina E/sangre , Japón/epidemiología , Masculino , Persona de Mediana Edad , Rinitis Alérgica Estacional/sangre , Adulto JovenRESUMEN
OBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.
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Tratamiento Conservador/métodos , Higiene/educación , Enfermedades de la Laringe/terapia , Educación del Paciente como Asunto/métodos , Pólipos/terapia , Evaluación de Programas y Proyectos de Salud , Femenino , Humanos , Enfermedades de la Laringe/patología , Laringoscopía/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pólipos/patología , Resultado del Tratamiento , Pliegues Vocales/patologíaRESUMEN
OBJECTIVE: To evaluate otologic features of primary ciliary dyskinesia (PCD), especially eardrum features, audiometric findings, and clinical course. STUDY DESIGN: Retrospective patient review. SETTING: Tertiary referral center. PATIENTS: Fifteen patients (mean age, 16.9 years [range, 1-32 yr]; 8 males and 7 females) diagnosed with PCD at our university hospital in the last 12 years. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Electron microscopy of nasal cilia, gene mutation analysis, endoscopy of 30 eardrums, pure-tone audiometry, and tympanometry. RESULTS: All 15 patients showed ciliary ultrastructural abnormalities on electron microscopy and/or biallelic mutations in genes associated with ciliary function or structure. All 30 eardrums examined showed certain abnormalities. Fourteen patients had otitis media with effusion or its sequelae. The remaining patient had chronic otitis media. Pure-tone audiometry revealed the mean air conduction thresholds to be 25.0 and 26.4âdB in the right and left ears, respectively. In the ears with better hearing and worse hearing, the mean air conduction thresholds were 22.3 and 29.0âdB respectively. CONCLUSION: Otologic disease among patients with PCD essentially comprised otitis media with effusion, and the patients' eardrums showed a variety of findings. Knowledge of these otologic features may lead to the early detection of PCD.
Asunto(s)
Síndrome de Kartagener/complicaciones , Otitis Media con Derrame/etiología , Otitis Media con Derrame/patología , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. METHODS: Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. RESULTS: Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive. CONCLUSIONS: TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.