Publications by authors named "Tomoko Sugiuchi"

10 Publications

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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

Cartilage Conduction Hearing Aid Fitting in Clinical Practice.

J Am Acad Audiol 2021 Jun 3. Epub 2021 Jun 3.

Department of Otolaryngology, Kochi Medical School, Kochi University, Oko-cho, Nankoku-shi, Kochi, Japan.

Background:  Cartilage conduction hearing aids (CCHAs) were newly devised and spread fast in Japan since their launch in 2017. However, little knowledge is available for this new device.

Purpose:  The aim of this study was to establish the knowledge of CCHAs and suggest their indication.

Research Design:  Correlational study.

Study Sample:  A total 256 patients were registered.

Data Collection And Analysis:  The fitting of CCHAs was surveyed in nine institutions. The outcomes were assessed by audiometric tests. The patients were classified into seven groups, depending on the ear conditions. The clinical characteristics, assessment results, and purchase rates were compared among the groups. The assessment results of CCHAs were also compared with those of previously used hearing aids.

Results:  Most patients who used CCHAs were classified into the bilateral closed (aural atresia or severe stenosis) ear ( = 65) or unilateral closed ear ( = 124) groups. The patients in these groups achieved good benefits that resulted in a high purchase rate. The bilateral continuous otorrhea group also supported a high purchase rate, although the benefits of CCHAs were not always excellent. In contrast, the purchase rate was poor in the patients who could use air conduction hearing aids (ACHAs) without absolute problems. As for using a CCHA as a contralateral routing of signals hearing aid, the benefits depended on the patients.

Conclusions:  CCHAs are considered as a great option not only to the patients with closed ears but also to those who had difficulties in ACHAs usage.
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http://dx.doi.org/10.1055/s-0041-1728758DOI Listing
June 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

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

Frequency and specific characteristics of the incomplete partition type III anomaly in children.

Laryngoscope 2017 07 31;127(7):1663-1669. Epub 2016 Aug 31.

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

Objectives/hypothesis: To determine the frequency of the incomplete partition type III anomaly and the genetic and clinical features associated with POU3F4 mutations in children with hearing loss.

Study Design: Retrospective case series from 2000 to 2014 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals.

Methods: A total of 1,004 patients (from 938 families) who had hearing loss by 10 years of age and had undergone computed tomography scanning of their temporal bones were enrolled in this genetic, clinical, and radiological study.

Results: The incomplete partition type III anomaly was identified in six patients (0.6%), each of whom had an enlargement of the vestibular aqueduct at the end close to the vestibule. The six patients also had POU3F4 variants, and a genetic analysis revealed frameshift deletions in three patients, a missense variant in two patients of the same family, and a large deletion in one patient. Three of the six patients with POU3F4 variants were sporadic cases, and in one patient the genetic mutation occurred de novo.

Conclusions: It was indicated that POU3F4 mutations can be predicted by incomplete partition type III anomaly by radiological examination of the inner ear. All six of the patients showed mixed hearing loss, but none showed fluctuations in hearing, which may be related to the lack of vestibular aqueduct enlargement at the operculum.

Level Of Evidence: 4 Laryngoscope, 127:1663-1669, 2017.
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http://dx.doi.org/10.1002/lary.26245DOI Listing
July 2017

Guidelines for the evaluation of hearing aid fitting (2010).

Auris Nasus Larynx 2016 Jun 2;43(3):217-28. Epub 2015 Dec 2.

Department of Otolaryngology, Hospital, National Rehabilitation Center for Persons with Disabilities, Japan.

Objective: The methods to evaluate the efficacy of the adjusted hearing aid for a hearing-impaired person are fitting tests. The tests include those presently carried out for evaluating hearing aid fitting, and the methods of testing and evaluation have been published as "Guidelines for the evaluation of hearing aid fitting (2010)" by the Japan Audiological Society.

Methods: Guidelines for the following 8 test methods are presented. (1) Measurements of speech performance-intensity functions and speech recognition scores; (2) Assessment of hearing aid fitting from the aspect of tolerance of environmental noise; (3) Measurement of real-ear insertion gain (measurement of sound pressure levels at the eardrum); (4) Measurement of the hearing threshold level and the uncomfortable loudness level (UCL) in sound pressure level (SPL) with an inserted earphone; (5) Aided threshold test in a sound field (functional gain measurement); (6) Prediction of insertion gain and aided threshold from hearing aid characteristics and the pure tone audiogram; (7) Measurement of speech recognition in noise; (8) Assessment of hearing aid fitting using questionnaires. In the above tests, (1) and (2) are mandatory tests, and (3) to (8) are informative tests.

Results: By performing test combinations properly selected from the above 8 tests, the benefits of a hearing aid could be determined.

Conclusion: The above test methods were useful and valuable in determining the efficacy of the adjusted hearing aid for a hearing-impaired person during clinical practice.
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http://dx.doi.org/10.1016/j.anl.2015.10.015DOI Listing
June 2016

[Complications Resulting from Taking Ear Impressions].

Nihon Jibiinkoka Gakkai Kaiho 2015 Aug;118(8):1058-67

In 2012, we carried out a study in a large sample to understand the secondary injuries caused during the taking ear impressions for hearing aids. This study is a follow-up of previous research conducted in 1986 (285 medical institutions) and 1999 (98 medical institutions). We posted a questionnaire survey to the otolaryngology departments of 3,257 medical institutions. The response rate to the questionnaire was 62.9% (2,050 of the 3,257 institutions), and the results indicated that 301 of the 2050 institutions (14.7%) had experience with secondary injuries, with a total of 460 cases reported. In 342 of the 460 cases (74.3%), the secondary injuries occurred at hearing-aid dealerships, followed by 67 cases (14.6%) at affiliated medical institutions, and 51 cases (11.1%) in other locations, including other medical institutions, rehabilitation counseling centers, and educational institutions. The most common type of secondary injury (298 cases, 64.8%) was caused by the presence of foreign bodies in the ear, which in turn was a result of complications occurring during the removal of residual ear impression material. Of these 298 cases, 32 required excision of the foreign bodies and surgical intervention under general anesthesia. The remaining 10 cases exhibited isolated tympanic membrane perforation without foreign body-related complications. Furthermore, 146 cases (31.7%) developed bleeding and otitis externa following removal of the ear impression, and there were reports of cases with bleeding that required long-term outpatient care and treatment. Therefore, since retention of a foreign body in the ear and tympanic membrane perforation can occur even in patients without a history of surgery or prior otologic history, adjustment of hearing aids requires prior otorhinolaryngological examination. Furthermore, because of the risk of secondary injury when taking ear impressions, this procedure must be performed with caution under the guidance of an otolaryngologist.
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http://dx.doi.org/10.3950/jibiinkoka.118.1058DOI Listing
August 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
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