The Heterozygous p.A684V Variant in the Gene Is a Mutational Hotspot Causing a Severe Hearing Loss Phenotype.

Background/objectives: A heterozygous mutation in the gene is responsible for autosomal dominant non-syndromic hearing loss (DFNA6/14/38) and Wolfram-like syndrome, which is characterized by bilateral sensorineural hearing loss with optic atrophy and/or diabetes mellitus. However, detailed clinical features for the patients with the heterozygous p.A684V variant remain unknown.

Detailed Clinical Features of -Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative variants have been reported to cause SNHL. However, the detailed clinical features of -associated hearing loss (HL) remain unclear.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation.

Successful cochlear implantation in a patient with Epstein syndrome during long-term follow-up.

Epstein syndrome is a rare disease characterized by macrothrombocytopenia, nephritis and progressive sensorineural hearing loss (SNHL). This syndrome is presently recognized as an autosomal dominant disease caused by mutations of non-muscle myosin heavy chain 9 (MYH9). Little information is available about the progress of SNHL, the efficacy of cochlear implants (CI) or the perioperative management of thrombocytopenia in patients with Epstein syndrome.

Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus.

We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Based on the level of chronic kidney disease-associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas.

Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes.

Frequency and clinical features of hearing loss caused by STRC deletions.

Sensorineural hearing loss is a common deficit and mainly occurs due to genetic factors. Recently, copy number variants (CNVs) in the STRC gene have also been recognized as a major cause of genetic hearing loss. We investigated the frequency of STRC deletions in the Japanese population and the characteristics of associated hearing loss.

Diagnostic pitfalls for -related hearing loss: A novel deletion detected by Array-CGH analysis in a Japanese patient with congenital profound hearing loss.

Here, we report a novel deletion (copy number variation: CNV) in the gene observed in a Japanese hearing loss patient. The deleted segment started in the middle of the gene, but the gene remained intact. This partial deletion in the gene highlights the need for further improvements in screening.

POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss.

A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population.

Round Window Application of an Active Middle Ear Implant: A Comparison With Hearing Aid Usage in Japan.

Objective: To report on the safety and efficacy of an investigational active middle ear implant (AMEI) in Japan, and to compare results to preoperative results with a hearing aid.

Design: Prospective study conducted in Japan in which 23 Japanese-speaking adults suffering from conductive or mixed hearing loss received a VIBRANT SOUNDBRIDGE with implantation at the round window. Postoperative thresholds, speech perception results (word recognition scores, speech reception thresholds, signal-to-noise ratio [SNR]), and quality of life questionnaires at 20 weeks were compared with preoperative results with all patients receiving the same, best available hearing aid (HA).

Facial nerve stimulation following cochlear implantation for X-linked stapes gusher syndrome leading to identification of a novel POU3F4 mutation.

We report a case of a nine-year-old male who presented with facial nerve stimulation four years after cochlear implantation. Computed tomography was performed revealing a dilated internal auditory meatus and the cochlear implant electrode was found to be protruding into the fallopian canal at the level of the geniculate ganglion. Subsequent genetic analysis demonstrated X-linked deafness type 2 (DFNX2) caused by a novel c.

[Evaluation of the Effectiveness and Safety in a Multi-center Clinical Trial of VIBRANT SOUNDBRIDGE in Japan].

Middle ear implants (MEIs) such as the Vibrant Soundbridge (VSB) are attractive and alternative treatments for patients with conductive, sensorineural, and mixed hearing loss who do not benefit from, or who choose not to wear, conventional hearing aids (HAs). Recent studies suggest that MEIs can provide better improvements in functional gain, speech perception, and quality of life than HAs, although there are certain risks associated with the surgery which should be taken into consideration, including facial nerve or chorda tympanic nerve damage, dysfunctions of the middle and inner ears, and future device failure/explantation. In Japan, a multi-center clinical trial of VSB was conducted between 2011-2014.

[Multicenter Clinical Study of Vibrant Soundbridge in Japan: Analysis of Subjective Questionnaires].

The Vibrant Soundbridge (VSB) is an active middle ear implant with the Floating Mass Transducer (FMT). We performed a multicenter study to study the efficacy of the VSB by means of "the 10 Questionnaire on Hearing 2002" and "the APHAB questionnaire" at 13 hospitals between 2011 and 2013. In all, 23 patients with mixed or conductive hearing loss received VSB implantation by the round window placement technique.

Frequency of Usher syndrome type 1 in deaf children by massively parallel DNA sequencing.

Usher syndrome type 1 (USH1) is the most severe of the three USH subtypes due to its profound hearing loss, absent vestibular response and retinitis pigmentosa appearing at a prepubescent age. Six causative genes have been identified for USH1, making early diagnosis and therapy possible through DNA testing. Targeted exon sequencing of selected genes using massively parallel DNA sequencing (MPS) technology enables clinicians to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis.

Prognostic impact of salvage treatment on hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic corticosteroids: A retrospective observational study.

Objective: To determine the prognostic factors for hearing recovery in patients with sudden sensorineural hearing loss (SSHL) refractory to systemic corticosteroids following salvage treatment.

Methods: This is a retrospective observational study at nine tertiary referral hospitals. A total of 120 patients with sudden deafness refractory to systemic corticosteroids were enrolled.

Discrimination of Japanese monosyllables in patients with high-frequency hearing loss.

Objective: To analyze the difficulty of discriminating Japanese nonsense monosyllables in each of several grades of high-frequency hearing loss and to evaluate the limitations of amplification.

Methods: We collected retrospective data on the discrimination of Japanese nonsense monosyllables by patients with three grades of high-frequency hearing loss who fulfilled or nearly fulfilled the Japanese criteria for EAS. Discrimination of the twenty monosyllables included in the 67-S speech audiometric test, which is approved by the Japan Audiological Society, was evaluated under quiet conditions.

Massively parallel DNA sequencing successfully identified seven families with deafness-associated MYO6 mutations: the mutational spectrum and clinical characteristics.

Objectives: To elucidate the involvement of MYO6 mutations, known to be responsible for DFNA22/DFNB37, in Japanese hearing loss patients through the use of genetic analysis.

Methods: Genomic variations responsible for hearing loss were identified by massively parallel DNA sequencing (MPS) of 63 target candidate genes in 1120 Japanese hearing loss patients, and the detailed clinical features for the patients with MYO6 mutations were collected and analyzed.

Results: Four mutations were successfully found in 7 families exhibiting autosomal dominant inheritance.

A case of fibrillary glomerulonephritis associated with thrombotic microangiopathy and anti-glomerular basement membrane antibody.

We present the first report of a case of fibrillary glomerulonephritis (FGN) associated with thrombotic microangiopathy (TMA) and anti-glomerular basement membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction.

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.

Background: To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.

Methods: We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients).

Hearing preservation and clinical outcome of 32 consecutive electric acoustic stimulation (EAS) surgeries.

Conclusions: Our results indicated that electric acoustic stimulation (EAS) is beneficial for Japanese-speaking patients, including those with less residual hearing at lower frequencies. Comparable outcomes for the patients with less residual hearing indicated that current audiological criteria for EAS could be expanded. Successful hearing preservation results, together with the progressive nature of loss of residual hearing in these patients, mean that minimally invasive full insertion of medium/long electrodes in cochlear implantation (CI) surgery is a desirable solution.

High-frequency involved hearing loss caused by novel mitochondrial DNA mutation in 16S ribosomal RNA gene.

Objective: To clarify the responsible gene for a family associated with hearing loss but having no well-known mitochondrial mutations.

Subjects: A Japanese family showing late-onset, progressive, and ski-sloping sensorineural hearing loss.

Results: Whole mitochondrial genome sequencing identified the 1673T>C mutation, a novel mitochondrial DNA mutation in the 16S ribosomal RNA gene.

Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1.

Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families.

OTOF mutation screening in Japanese severe to profound recessive hearing loss patients.

Background: Auditory neuropathy spectrum disorder (ANSD) is a unique form of hearing loss that involves absence or severe abnormality of auditory brainstem response (ABR), but also the presence of otoacoustic emissions (OAEs). However, with age, the OAEs disappear, making it difficult to distinguish this condition from other nonsyndromic hearing loss. Therefore, the frequency of ANSD may be underestimated.