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. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Analysis of outcomes for communication mode in cochlear implant in prelingually deafened adults.

OBJECTIVE: Recent studies have suggested that speech perception outcomes after cochlear implantation (CI) in prelingually deafened adults have improved with advances in CI technology and speech processing strategies. However, the outcomes vary from case to case. Communication mode has been reported in many studies as the factor that related to the post CI outcomes. This study aimed at investigating the post CI outcomes and the progress during 2 years for each communication mode. MATERIAL AND METHODS: The subjects were 17 prelingually deafened adults undergoing CI at our hospital between April 2013 and March 2019. We investigated preoperative factors affecting post CI outcomes. Also we analyzed post CI outcomes for each communication mode and compared preoperative factors for each communication mode. RESULTS: Communication mode and preoperative discrimination score were the factor affecting on postoperative discrimination score. The speech perception score after CI improved significantly in the oral and lip-reading group and total communication group. The speech perception scores in postlingually deafened adults improved significantly during the first six months and became to plateau after CI. On the other hand, the scores of prelingually deafened adults tended to improve gradually after six months postoperatively. Furthermore, the degree of improvement and progress differed by each communication mode. CONCLUSION: The communication mode is important factors in predicting outcomes in prelingually deafened adults after CI. Long-term auditory training is important for prelingually deafened adults who use visual information as their preoperative method of communication.

Speech Perception in Noise and Sound Localization for Cochlear Implant With Single-Sided Deafness Compared With Contralateral Routing of Signal Hearing Aids.

OBJECTIVE: Cochlear implantation (CI) for the treatment of single-sided deafness (SSD) is a relatively new treatment modality. Although comparing the effectiveness of CI and contralateral routing of signal (CROS) hearing aids (HAs) is important, very few reports on this topic exist. In this study, objective assessments and subjective assessments were conducted to determine which SSD individuals would prefer CI or CROS HAs. MATERIALS AND METHODS: Objective assessments (speech perception and sound localization) and subjective assessments (Hearing Handicap Inventory for Adults (HHIA), Abbreviated Profile of Hearing Aid Benefit (APHAB), MOS Short-Form 36-Item Health Survey version 2 (SF-36v2)) were performed on 87 SSD patients. Of the 87 SSD patients, 33 patients hoped for CROS HAs, and 17 patients hoped for CI. The CI group underwent subjective and objective assessments at 6 and 12 months postoperatively. The CROS HAs group underwent objective assessments at 1 month after wearing CROS HAs. RESULTS: After the intervention, the localization ability was significantly improved in the CI group (p < 0.05) with no significant improvement in that of the CROS HAs group (p = 0.48). No significant improvement in speech perception in noise was observed in the CROS (Signal-to-Noise ratio + 10, p = 0.08; SN + 0, p = 0.17); however, a significant improvement in the CI group was observed at 12 months postoperatively. The APHAB subscale "background noise" and SF-36v2 health concepts of role-physical, general health, vitality, role-emotional, and mental health were significantly higher in the CI group. CONCLUSION: CI was superior to CROS HAs in speech perception in terms of noise and sound localization. Patients with postlingual acute-onset hearing loss and more handicaps and a more positive view of their hearing loss possibly tend to choose CI.

Active middle ear implant (vibrant soundbridge) in children with unilateral congenital aural atresia.

BACKGROUND: Detailed studies have not been conducted on sound localization and speech perception in noise in patients with unilateral congenital aural atresia (UCAA). AIMS/OBJECTIVES: To evaluate the benefits of the use of the Vibrant Soundbridge (VSB) for UCAA by performing audiometric and sound localization tests. MATERIALS AND METHODS: Four children with UCAA underwent VSB (VORP 503) implantation from 2018 to 2019. Speech perception tests in noise were conducted using the Japanese monosyllable test. The spatial configuration for speech testing consisted of speech presented from the front and noise presented into the normal ear (S0N90). The sound localization test was conducted using nine loudspeakers equally distributed in a semicircle. RESULTS: The children's speech perception in noise 6 months after VSB activation was significantly better than before activation (p < .05). Additionally, the children's sound localization ability after VSB activation was significantly better than before VSB activation. CONCLUSION AND SIGNIFICANCE: The benefits of VSB use in children with UCAA were revealed using audiometric and sound localization tests.

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. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

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. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands) to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants) were successfully identified in 15 probands (2.5%) among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants in POU4F3 were a common cause of autosomal dominant HL.

Clinical profile of hearing loss in children with congenital cytomegalovirus (CMV) infection: CMV DNA diagnosis using preserved umbilical cord.

CONCLUSIONS: Congenital cytomegalovirus (CMV) infection is a major cause of bilateral and unilateral sensorineural hearing loss (SNHL) in children, accounting for 9.0% of SNHL cases. The diagnostic rate using combined genetic deafness test and CMV DNA detection test was determined to be 46.4% in bilateral profound SNHL. OBJECTIVES: The present study investigated the prevalence of congenital CMV infection diagnosed retrospectively by detection of CMV DNA in dried umbilical cord specimens from children with unilateral or bilateral SNHL up to the age of 12 years. METHODS: Preserved dried umbilical cords were collected from 134 children with bilateral (46 children) or unilateral (88 children) SNHL. DNA was extracted from the dried umbilical cords and CMV DNA was detected by quantitative PCR. Genetic deafness tests based on the invader assay were performed in children with bilateral SNHL. RESULTS: CMV DNA from the dried umbilical cords was detected in 8.7% of the bilateral SNHL and 9.1% of unilateral SNHL. Deafness gene mutations were identified in 21.7% (10/46) of children with bilateral SNHL.