Publications by authors named "Sawako Masuda"

43 Publications

Investigation of the hearing levels of siblings affected by a single GJB2 variant: Possibility of genetic modifiers.

Int J Pediatr Otorhinolaryngol 2021 Oct 12;149:110840. Epub 2021 Jul 12.

Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan; Medical Genetics Center, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. Electronic address:

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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http://dx.doi.org/10.1016/j.ijporl.2021.110840DOI Listing
October 2021

Primary cytomegalovirus infection during pregnancy and congenital infection: a population-based, mother-child, prospective cohort study.

J Perinatol 2021 Jul 20. Epub 2021 Jul 20.

Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

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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http://dx.doi.org/10.1038/s41372-021-01157-9DOI Listing
July 2021

A pediatric case of productive cough caused by novel variants in DNAH9.

Hum Genome Var 2021 Jan 15;8(1). Epub 2021 Jan 15.

Institute for Clinical Research, National Hospital Organization Mie National Hospital, Tsu, Mie, Japan.

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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http://dx.doi.org/10.1038/s41439-020-00134-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810879PMC
January 2021

Differences in hearing levels between siblings with hearing loss caused by GJB2 mutations.

Auris Nasus Larynx 2020 Dec 15;47(6):938-942. Epub 2020 Jun 15.

Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan; Medical Genetics Center, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo 152-8902, Japan. Electronic address:

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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http://dx.doi.org/10.1016/j.anl.2020.05.008DOI Listing
December 2020

Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause hereditary hearing loss in humans.

PLoS Genet 2020 04 15;16(4):e1008643. Epub 2020 Apr 15.

Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro, Tokyo, Japan.

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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http://dx.doi.org/10.1371/journal.pgen.1008643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159186PMC
April 2020

Comparison of the prevalence and features of inner ear malformations in congenital unilateral and bilateral hearing loss.

Int J Pediatr Otorhinolaryngol 2019 Oct 28;125:92-97. Epub 2019 Jun 28.

Department of Otorhinolaryngology, Institute for Clinical Research, National Hospital Organization Mie National Hospital, Tsu, Mie, Japan.

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%]; p = 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%]; p < 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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http://dx.doi.org/10.1016/j.ijporl.2019.06.028DOI Listing
October 2019

Vocal Hygiene Education Program Reduces Surgical Interventions for Benign Vocal Fold Lesions: A Randomized Controlled Trial.

Laryngoscope 2018 11 6;128(11):2593-2599. Epub 2018 Aug 6.

Department of Otolaryngology, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan.

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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http://dx.doi.org/10.1002/lary.27415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585860PMC
November 2018

Analysis of factors associated with cedar pollen sensitization and development of pollinosis in a young Japanese adult population.

Allergol Int 2019 Jan 13;68(1):39-45. Epub 2018 Jun 13.

Department of Otorhinolaryngology, Head & Neck Surgery, Mie University Graduate School of Medicine, Mie, Japan. Electronic address:

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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http://dx.doi.org/10.1016/j.alit.2018.05.006DOI Listing
January 2019

Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

Ear Hear 2019 Jan/Feb;40(1):184-191

Division of Hearing and Balance Research, National Institute for Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

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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http://dx.doi.org/10.1097/AUD.0000000000000586DOI Listing
April 2019

Analysis of Otologic Features of Patients With Primary Ciliary Dyskinesia.

Otol Neurotol 2017 12;38(10):e451-e456

*Department of Otorhinolaryngology, Head and Neck Surgery, Mie University Graduate School of Medicine †Department of Otorhinolaryngology, Mie National Hospital ‡Electron Microscopy Research Center §Central Clinical Laboratories, Mie University Graduate School of Medicine ||Institute for Clinical Research, Mie National Hospital ¶Division of Personalized Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

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 26.4 dB 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 29.0 dB 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.
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http://dx.doi.org/10.1097/MAO.0000000000001599DOI Listing
December 2017

Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss.

Orphanet J Rare Dis 2017 09 25;12(1):157. Epub 2017 Sep 25.

Department of Otolaryngology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo, 152-8902, Japan.

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.
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http://dx.doi.org/10.1186/s13023-017-0708-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613382PMC
September 2017

Sonographic diagnosis of acute mastoiditis and subsequent retroauricular abscess in a pediatric cochlear implant recipient: A case report.

J Clin Ultrasound 2017 Oct 3;45(8):515-519. Epub 2017 Apr 3.

Department of Otorhinolaryngology-Head & Neck Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

When acute mastoiditis occurs in cochlear implant recipients, it can progress to subsequent retroauricular abscess due to the absence of the external mastoid cortex resulting from mastoidectomy performed for cochlear implantation. The management goal is to control infection while preserving the implanted device. A 2-year-old boy with cochlear implants developed acute mastoiditis and a subsequent retroauricular abscess. The patient underwent a surgical intervention based on the diagnosis made utilizing gray-scale and power Doppler sonography. This case illustrates the diagnostic usefulness of sonography in this rare situation. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:515-519, 2017.
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http://dx.doi.org/10.1002/jcu.22442DOI Listing
October 2017

WFS1 and GJB2 mutations in patients with bilateral low-frequency sensorineural hearing loss.

Laryngoscope 2017 09 8;127(9):E324-E329. Epub 2017 Mar 8.

Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

Objective: Evaluating the prevalence of specific gene mutations associated with a certain audiometric configuration facilitates clinical assessment of patients with sensorineural hearing loss (SNHL). WFS1 is responsible for autosomal dominant nonsyndromic deafness 6/14/38 and is the most frequent genetic cause of low-frequency SNHL (LFSNHL); however, the exact prevalence of WFS1 mutations in LFSNHL is unknown. Therefore, we evaluated genetic mutations and clinical features in patients with nonsyndromic bilateral LFSNHL, focusing on the WFS1.

Study Design: Retrospective case series from 2002 to 2013 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals.

Methods: WFS1, GJB2, and mitochondrial DNA mutation screening was carried out for 74 of 1,007 Japanese probands with bilateral LFSNHL.

Results: WFS1 and GJB2 mutations were identified in eight of 74 cases (10.8%). Four cases had heterozygous WFS1 mutations; one case had a heterozygous WFS1 mutation and a heterozygous GJB2 mutation; and three cases had biallelic GJB2 mutations. Three cases with WFS1 mutations were sporadic; two of them were confirmed to be caused by a de novo mutation based on the genetic analysis of their parents. In the case with mutations in both WFS1 and GJB2, a de novo mutation of WFS1 was confirmed in the proband's mother by genetic screening of the mother's parents.

Conclusion: Genetic screening focusing on LFSNHL has not been conducted. The present study first revealed the prevalence of specific gene mutations. WFS1 autosomal dominant mutations were identified even in sporadic cases. Our results also suggested a mutational hotspot in WFS1.

Level Of Evidence: 4. Laryngoscope, 127:E324-E329, 2017.
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http://dx.doi.org/10.1002/lary.26528DOI Listing
September 2017

Sensitization to secretoglobin and lipocalins in a group of young children with risk of developing respiratory allergy.

Clin Mol Allergy 2017 3;15. Epub 2017 Mar 3.

Allergy Center and Department of Clinical Research, Mie National Hospital, IDD, Tsu, Mie Japan.

Background: Multiple sensitizations in early age have been reported to be a risk for development of asthma. This study evaluates the emergence and evolution of IgE to aeroallergens among a cohort of children with physician-diagnosed atopic dermatitis and/or showing food allergy symptoms and to examine the relation to asthma development.

Methods: Three-hundred and four children (median age 13.4 months at entry) with food allergy symptoms and/or atopic dermatitis without asthma at inclusion were analysed for IgE antibodies against food-, indoor- and outdoor-allergens and pet allergen components and correlated to the individuals' outcome on asthma inception.

Results: At 2 years of follow-up, physician-diagnosed asthma was 19.7% (n = 49) and asthma diagnosed any time was 24% (n = 67). History of persistent cough and asthma of father, combination of milk- and wheat-allergy symptoms and dual sensitization to house dust mite and Japanese cedar were independent risk factors for asthma. Sensitization to dog was the most prevalent inhalant allergen at entry. Asthma children had a higher proportion of sensitization to dog, cat and horse allergens at entry compared with non-asthma children. Being sensitized to both food, house dust mite and pet allergens was strongly associated with asthma (p = 0.0006). Component resolved diagnosis for dog and cat allergens showed that IgE antibodies to Can f 1 and Fel d 1 was common even at very young age.

Conclusions: Early sensitization to inhalant allergens increases the risk of developing asthma as well as having milk and wheat allergy symptoms. Sensitization to dog, was common at an early age despite dog ownership. Sensitization to secretoglobin and lipocalins and less to serum albumins explained the pet sensitization.
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http://dx.doi.org/10.1186/s12948-017-0061-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335719PMC
March 2017

Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

Clin Rehabil 2017 Aug 14;31(8):1049-1056. Epub 2016 Oct 14.

1 Department of Artificial Organs and Medical Device Creation, National Institute of Sensory Organs, Tokyo, Japan.

Objectives: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency.

Design: Parallel-arm, individual randomized controlled trial.

Methods: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups.

Results: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001).

Conclusion: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly.

Clinical Trial: gov Identifier-UMIN000015567.
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http://dx.doi.org/10.1177/0269215516673208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524188PMC
August 2017

EPIDEMIOLOGY AND CLINICAL FEATURE OF ALLERGIC RHINITIS IN CHILDREN.

Authors:
Sawako Masuda

Arerugi 2016 08;65(8):990-3

Department of Otorhinolaryngology, National Mie Hospital.

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http://dx.doi.org/10.15036/arerugi.65.990DOI Listing
August 2016

Novel syndrome with conductive hearing loss and congenital glaucoma in three generations.

Auris Nasus Larynx 2017 Aug 21;44(4):493-497. Epub 2016 Aug 21.

Department of Otorhinolaryngology, Mie National Hospital, Tsu, Japan.

The objective of this paper was to describe the clinical and otological findings in multiple members of a family with congenital glaucoma, cardiac anomaly, and conductive hearing loss due to ossicular chain anomalies. We performed a retrospective review of the medical charts and otological materials of multiple members of the same family. Congenital glaucoma and hearing loss were inherited by the proband and her daughter, son, and mother, suggesting autosomal dominant inheritance. The son and daughter also showed atrial septal defects. Exploratory tympanotomies revealed anomalies of the long process of the incus in the proband and her daughter, and tympanoplasty improved hearing loss in both patients. This represents the first description of coexisting congenital glaucoma and conductive hearing loss due to ossicular chain anomalies in multiple members of a single family.
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http://dx.doi.org/10.1016/j.anl.2016.08.001DOI Listing
August 2017

Recent advances in primary ciliary dyskinesia.

Auris Nasus Larynx 2016 Jun 31;43(3):229-36. Epub 2015 Oct 31.

Institute for Clinical Research, Mie National Hospital, Tsu, Japan.

Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.
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http://dx.doi.org/10.1016/j.anl.2015.09.012DOI Listing
June 2016

SYMPTOMS AND HINDRANCES DUE TO PEDIATRIC JCP EVALUATED BY PATIENTS AND THEIR PARENTS.

Arerugi 2015 07;64(7):942-51

Department of Otorhinolaryngology, National Mie Hospital.

Background: It is difficult to know how the children with Japanese cedar pollinosis (JCP) recognize their own symptoms and quality of life (QOL). In addition, the adversely impact of pediatric JCP on the QOL of the parents is not understood. The aim of this study was to investigate the symptoms and troubles due to pediatric JCP evaluated by patients and their parents, and analyze the difference.

Methods: Twenty-six pair of children (7-15 years of age) with JCP and their parents/grandparents who visited our ENT clinic filled out questionnaire regarding the symptoms and hindrances due to JCP.

Results: There were significantly correlations between the severity of symptoms evaluated by children and parents/grandparents. The most frequent problem was "rubbing nose and eyes", both in children and parents/grandparents. The children were tended to be troubled by practical problems. The parents/grandparents were tended to be worried about the emotion, sleep and activity in daily life and health condition of their children. The total nasal symptom score was significantly higher in children of parents/grandparents with the anxiety about the health condition than in ones without the anxiety.

Conclusions: The school age children with JCP can express their symptom appropriately. There is a different tendency in hindrances due to pediatric JCP between in patients and parents/grandparents. It is necessary to develop the QOL questionnaire sheets for children with allergic rhinitis and their parents.
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http://dx.doi.org/10.15036/arerugi.64.942DOI Listing
July 2015

A novel frameshift mutation in KCNQ4 in a family with autosomal recessive non-syndromic hearing loss.

Biochem Biophys Res Commun 2015 Aug 31;463(4):582-6. Epub 2015 May 31.

Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo 152-8902, Japan; Medical Genetics Center, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo 152-8902, Japan. Electronic address:

Mutation of KCNQ4 has been reported to cause autosomal dominant non-syndromic hearing loss (DFNA2A) that usually presents as progressive hearing loss starting from mild to moderate hearing loss during childhood. Here, we identified a novel KCNQ4 mutation, c.1044_1051del8, in a family with autosomal recessive non-syndromic hearing loss. The proband was homozygous for the mutation and was born to consanguineous parents; she showed severe hearing loss that was either congenital or of early childhood onset. The proband had a sister who was heterozygous for the mutation but showed normal hearing. The mutation caused a frameshift that eliminated most of the cytoplasmic C-terminus, including the A-domain, which has an important role for protein tetramerization, and the B-segment, which is a binding site for calmodulin (CaM) that regulates channel function via Ca ions. The fact that the heterozygote had normal hearing indicates that sufficient tetramerization and CaM binding sites were present to preserve a normal phenotype even when only half the proteins contained an A-domain and B-segment. On the other hand, the severe hearing loss in the homozygote suggests that complete loss of the A-domain and B-segment in the protein caused loss of function due to the failure of tetramer formation and CaM binding. This family suggests that some KCNQ4 mutations can cause autosomal recessive hearing loss with more severe phenotype in addition to autosomal dominant hearing loss with milder phenotype. This genotype-phenotype correlation is analogous to that in KCNQ1 which causes autosomal dominant hereditary long QT syndrome 1 with milder phenotype and the autosomal recessive Jervell and Lange-Nielsen syndrome 1 with more severe phenotype due to deletion of the cytoplasmic C-terminus of the potassium channel.
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http://dx.doi.org/10.1016/j.bbrc.2015.05.099DOI Listing
August 2015

High prevalence of CDH23 mutations in patients with congenital high-frequency sporadic or recessively inherited hearing loss.

Orphanet J Rare Dis 2015 May 13;10:60. Epub 2015 May 13.

Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan.

Background: Mutations in CDH23 are responsible for Usher syndrome 1D and recessive non-syndromic hearing loss. In this study, we revealed the prevalence of CDH23 mutations among patients with specific clinical characteristics.

Methods: After excluding patients with GJB2 mutations and mitochondrial m.1555A > G and m.3243A > G mutations, subjects for CDH23 mutation analysis were selected according to the following criteria: 1) Sporadic or recessively inherited hearing loss 2) bilateral non-syndromic congenital hearing loss, 3) no cochlear malformation, 4) a poorer hearing level at high frequencies than at low frequencies, and 5) severe or profound hearing loss at higher frequencies.

Results: Seventy-two subjects were selected from 621 consecutive probands who did not have environmental causes for their hearing loss. After direct sequencing, 13 of the 72 probands (18.1%) had homozygous or compound heterozygous CDH23 mutations. In total, we identified 16 CDH23 mutations, including five novel mutations. The 16 mutations included 12 missense, two frameshift, and two splice-site mutations.

Conclusions: These results revealed that CDH23 mutations are highly prevalent in patients with congenital high-frequency sporadic or recessively inherited hearing loss and that the mutation spectrum was diverse, indicating that patients with these clinical features merit genetic analysis.
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http://dx.doi.org/10.1186/s13023-015-0276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451718PMC
May 2015

Changes of micro-RNAs in asymptomatic subjects sensitized to Japanese cedar pollen after prophylactic sublingual immunotherapy.

Allergy Rhinol (Providence) 2015 Jan 11;6(1):33-8. Epub 2015 Feb 11.

Department of Otorhinolaryngology, Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Japanese cedar pollinosis is the predominant seasonal allergic rhinitis in Japan, and it has increased in prevalence during the past 10 years. Sublingual immunotherapy (SLIT) is considered a safe and effective treatment for pollinosis. Micro-RNAs (miRNAs) are a class of short single-stranded RNA molecules that posttranscriptionally silence gene expression and may mediate allergic immune responses. The aim of this study was to investigate the miRNA alteration in asymptomatic subjects sensitized to Japanese cedar pollen under prophylactic SLIT under part of a randomized, double-blind, placebo-controlled, multiple-center trial. Analysis was undertaken in 15 asymptomatic subjects sensitized to Japanese cedar pollen-specific IgE (ImmunoCAP class ≥2) who participated in 2013. The SLIT group (n = 6) received standardized Japanese cedar pollen extract and the placebo group (n = 9) received an inactive placebo for 5 months covering the cedar pollen season. Changes in serum miRNAs were measured by real-time quantitative polymerase chain reaction to determine whether SLIT had effects on profiles of circulating miRNA. Seven subjects in the placebo group developed pollinosis symptoms, whereas no subjects in the SLIT group did (p = 0.007). Serum hsa-miR-223 was significantly up-regulated in postseason compared with preseason samples. The hsa-let-7b was significantly more down-regulated in postseason than in preseason samples from the placebo group; however, no significant differences were observed in those from the SLIT group. A significant decrease in circulating let-7b was also observed in the subjects who developed symptoms. Prophylactic SLIT was effective in preventing the development of pollinosis. Alterations in miRNA expression occurred in asymptomatic, sensitized subjects during cedar pollen season.
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http://dx.doi.org/10.2500/ar.2015.6.0107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388874PMC
January 2015

Immunological parameters in prophylactic sublingual immunotherapy in asymptomatic subjects sensitized to Japanese cedar pollen.

Allergol Int 2015 Jan 20;64(1):54-9. Epub 2014 Oct 20.

Department of Otorhinolaryngology, Head & Neck Surgery, Mie University Graduate School of Medicine, Mie, Japan. Electronic address:

Background: This study aims to examine the immunological parameters, focusing IL-10 productivity, in prophylactic sublingual immunotherapy (SLIT) in asymptomatic subjects sensitized to Japanese cedar pollen (JCP).

Methods: This study was conducted as part of a randomized, double-blind, placebo-controlled, multiple center trial, and was performed for two consecutive pollen seasons in 2012 and 2013. The present results were based only on our institution. We recruited 29 participants with specific IgE against JCP of at class 2 and higher levels without history of the pollinosis symptoms at the time of JCP scattering. The SLIT group received standardized JCP extract for five months over the pollen season. We observed and judged development of the symptoms in the pollen season. The percentage of IL-10 producing CD4(+) T (Trl) cells, B cells and monocytes were analyzed by flow cytometry. JCP specific IgE and total IgE were also measured.

Results: The ratio of development of cedar pollinosis was significantly lower in the SLIT group compared to the placebo group in 2013. In 2012, the percentage of circulating Tr1 cells and IL-10 producing monocytes significantly increased in the SLIT group. In 2013, the percentage of circulating Tr1 cells and IL-10 producing B cells increased significantly in the SLIT group. The percentage of circulating IL-10 producing monocytes significantly decreased in the placebo group.

Conclusions: Prophylactic SLIT is effective for prevention of the development of pollinosis. Induction of IL-10 producing T cells, B cells and monocytes is an important mechanism of SLIT for prevention of pollinosis in asymptomatic but sensitized subjects.
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http://dx.doi.org/10.1016/j.alit.2014.07.001DOI Listing
January 2015

Measurement of Japanese cedar pollen-specific IgE in nasal secretions.

Allergol Int 2014 Sep;63(3):467-73

Department of Otorhinolaryngology, Head & Neck Surgery, Mie University Graduate School of Medicine, Mie, Japan.

Background: Japanese cedar pollen (JCP) is the most common allergen for seasonal allergic rhinitis in Japan. Little is known about local production of immunoglobulin (Ig)E in people with or without Japanese cedar pollinosis. The aims of this study were to measure levels of JCP-specific IgE in nasal secretions and determine correlations with levels in serum.

Methods: Forty-six subjects were enrolled in this study, comprising 24 symptomatic subjects, 9 asymptomatic subjects sensitized to JCP, and 13 subjects not sensitized to JCP. Nasal secretions were obtained during a period of Japanese cedar dispersal, and levels of JCP-specific IgE were measured with CAP-fluorescent enzyme immunoassay. Serum JCP-specific IgE and total IgE were also measured using the same method.

Results: Among the 46 subjects enrolled, JCP-specific IgE in nasal secretions was measureable in 43 subjects. Irrespective of symptom development, sensitized subjects showed higher levels of JCP-specific IgE in nasal secretions than non-sensitized subjects. A significant moderate correlation was observed between JCP-specific IgE levels in nasal secretions and serum in all 43 subjects. With stratification by subject group, only symptomatic subjects showed a substantial correlation between JCP-specific IgE levels in nasal secretions and serum.

Conclusions: Our results imply a certain association between JCP-specific IgE in nasal secretions and sensitization of Japanese cedar pollinosis. Therefore, levels of allergen-specific IgE in nasal secretions can be used as an alternative diagnostic marker for allergic rhinitis patients.
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http://dx.doi.org/10.2332/allergolint.13-OA-0668DOI Listing
September 2014

A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss.

Biochem Biophys Res Commun 2014 May 13;447(3):496-502. Epub 2014 Apr 13.

Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan. Electronic address:

The access of bone morphogenetic protein (BMP) to the BMP receptors on the cell surface is regulated by its antagonist noggin, which binds to heparan-sulfate proteoglycans on the cell surface. Noggin is encoded by NOG and mutations in the gene are associated with aberrant skeletal formation, such as in the autosomal dominant disorders proximal symphalangism (SYM1), multiple synostoses syndrome, Teunissen-Cremers syndrome, and tarsal-carpal coalition syndrome. NOG mutations affecting a specific function may produce a distinct phenotype. In this study, we investigated a Japanese pedigree with SYM1 and conductive hearing loss and found that it carried a novel heterozygous missense mutation of NOG (c.406C>T; p.R136C) affecting the heparin-binding site of noggin. As no mutations of the heparin-binding site of noggin have previously been reported, we investigated the crystal structure of wild-type noggin to investigate molecular mechanism of the p.R136C mutation. We found that the positively charged arginine at position 136 was predicted to be important for binding to the negatively charged heparan-sulfate proteoglycan (HSPG). An in silico docking analysis showed that one of the salt bridges between noggin and heparin disappeared following the replacement of the arginine with a non-charged cysteine. We propose that the decreased binding affinity of NOG with the p.R136C mutation to HSPG leads to an excess of BMP signaling and underlies the SYM1 and conductive hearing loss phenotype of carriers.
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http://dx.doi.org/10.1016/j.bbrc.2014.04.015DOI Listing
May 2014

'Benifuuki' green tea containing o-methylated catechin reduces symptoms of Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.

Allergol Int 2014 Jun 25;63(2):211-7. Epub 2014 Feb 25.

Department of Clinical Research, Mie National Hospital, Mie, Japan.

Background: Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP).

Methods: The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season.

Results: Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group.

Conclusions: 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.
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http://dx.doi.org/10.2332/allergolint.13-OA-0620DOI Listing
June 2014

'Benifuuki' Green Tea Containing O-Methylated Catechin Reduces Symptoms of Japanese Cedar Pollinosis: A Randomized, Double- Blind, Placebo-Controlled Trial.

Allergol Int 2014 27;63(2):211-217. Epub 2015 Feb 27.

Department of Clinical Research. Electronic address:

Background: Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP).

Methods: The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700 ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season.

Results: Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group.

Conclusions: 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.
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http://dx.doi.org/10.2332/allergolint.13-OA-0620DOI Listing
February 2015

Subgroups of enlarged vestibular aqueduct in relation to SLC26A4 mutations and hearing loss.

Laryngoscope 2014 Apr 17;124(4):E134-40. Epub 2013 Dec 17.

Department of Otolaryngology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Otorhinolaryngology, Inagi Municipal Hospital, Tokyo, Japan; Department of Otolaryngology, Keio University Hospital, Tokyo, Japan.

Objectives/hypothesis: To investigate possible association of hearing loss and SLC26A4 mutations with the subgroups of enlarged vestibular aqueduct (EVA) morphology in Japanese subjects with hearing loss.

Study Design: Retrospective multicenter study.

Methods: Forty-seven subjects who had vestibular aqueduct with midpoint diameter >1 mm by computed tomography of the temporal bone were enrolled at multiple sites across Japan, and DNA samples and clinical data were collected. EVA morphology was classified into four subgroups by the pattern of enlargement: aperture, aperture and midpoint, midpoint, and borderline enlargement. Venous blood DNA samples were subjected to polymerase chain reaction-based direct sequencing of all exons and exon-intron boundaries of the SLC26A4.

Results: Four novel SLC26A4 mutations were identified in the present study. SLC26A4 mutations were detected in almost all subjects with aperture, aperture and midpoint, and midpoint enlargement. In contrast, 71% of subjects with borderline enlargement had no SLC26A4 mutation. No significant difference was found in the distribution of truncating and nontruncating SLC26A4 mutations between the EVA subgroups. In addition, no significant correlation was observed between the EVA subgroups and hearing levels, incidence of hearing fluctuation, or progression of hearing loss.

Conclusions: Subgroups of EVA morphology were significantly correlated with the presence or absence of SLC26A4 mutation. In a subgroup analysis of subjects with SLC26A4 mutations, however, differences in the EVA subgroups were not correlated with SLC26A4 genotypes or characteristics of hearing loss.

Level Of Evidence: NA.
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http://dx.doi.org/10.1002/lary.24368DOI Listing
April 2014

GJB2-associated hearing loss undetected by hearing screening of newborns.

Gene 2013 Dec 6;532(1):41-5. Epub 2013 Sep 6.

Department of Otolaryngology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

The hearing loss caused by GJB2 mutations is usually congenital in onset, moderate to profound in degree, and non-progressive. The objective of this study was to study genotype/phenotype correlations and to document 14 children with biallelic GJB2 mutations who passed newborn hearing screening (NHS). Genetic testing for GJB2 mutations by direct sequencing was performed on 924 individuals (810 families) with hearing loss, and 204 patients (175 families) were found to carry biallelic GJB2 mutations. NHS results were obtained through medical records. A total of 18 pathological mutations were identified, which were subclassified as eight inactivating and 10 non-inactivating mutations. p.I128M and p.H73Y were identified as novel missense GJB2 mutations. Of the 14 children with biallelic GJB2 mutations who passed NHS, eight were compound heterozygotes and 3 were homozygous for the c.235delC mutation in GJB2, and the other three combinations of non-c.235delC mutations identified were p.Y136X-p.G45E/p.V37I heterozygous, c.512ins4/p.R143W heterozygous, and p.V37I/p.R143W heterozygous. These 14 cases demonstrate that the current NHS does not identify all infants with biallelic GJB2 mutations. They suggest that the frequency of non-penetrance at birth is approximately 6.9% or higher in DFNB1 patients and provide further evidence that GJB2 hearing loss may not always be congenital in onset.
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http://dx.doi.org/10.1016/j.gene.2013.08.094DOI Listing
December 2013

Analysis of factors influencing sensitization of Japanese cedar pollen in asymptomatic subjects.

Auris Nasus Larynx 2013 Dec 8;40(6):543-7. Epub 2013 May 8.

Department of Otorhinolaryngology, Head & Neck Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

Objective: Japanese cedar pollinosis is increasing rapidly in Japan. Although analysis has been made concerning the factors influencing the development of the cedar pollinosis, analysis concerning the risk factors influencing the sensitization in asymptomatic subjects has not been done.

Methods: Risk factors for sensitization to Japanese cedar pollen were analyzed among 73 subjects (32 men and 41 women) who do not develop symptoms of pollinosis at the time of Japanese cedar pollen scattering. Their ages ranged from 18 to 60 years with the mean of 34.1 years. Possible factors influencing sensitization were investigated through a written questionnaire and doctors' questioning. Japanese cedar-specific IgE titers and Dermatophagoides pteronyssinus-specific IgE titers in the serum were measured by CAP-FEIA (fluorescent enzyme immunoassay).

Results: Of the 73 subjects, 26 were sensitized to the Japanese cedar pollen, for a 36% sensitization rate. Among the eleven factors examined, only one factor was shown to significantly influence the sensitization rate to Japanese cedar pollen. It was sensitization to house dust mites (56.5% vs. 26.0% χ(2) value=6.27, p=0.012). The sensitization rate to the pollen did not correlate to the presence of other allergic diseases, history of rhinosinusitis, family history of Japanese cedar pollinosis, food preference, presence or absence of cedar trees in the surroundings, present living circumstances, childhood circumstances, age, sex, or smoking habits. We calculated odds ratios in order to estimate how much those factors influence the sensitization to Japanese cedar pollen. Significantly high odds ratio for sensitization to house dust mite (6.63; 95% confidence interval (CI): 1.76-32.2) was found.

Conclusion: The present study indicates that sensitization to the pollen in the subjects without pollinosis is influenced by sensitization to house dust mite.
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http://dx.doi.org/10.1016/j.anl.2013.04.001DOI Listing
December 2013
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