Gene analysis is an essential tool in medical diagnostics, and the next-generation sequencer (NGS) plays an important role. A rapid and exhaustive analysis is available with the NGS, which provides a massively parallel sequencing. However, NGS identifies an enormous number of variants, and adequate professional knowledge is required for the evaluation of their pathogenicity. Target sequencing for 63 deafness genes, followed by social health insurance-based screening for cases with any of 154 mutations in 19 deafness genes, usually reveals 300 to 400 variants in a patient. First, the variants are filtered by their allele frequencies, locations/types, and in silico analysis results. Second, the pathogenicity of the remaining variants is evaluated according to the American College of Medical Genetics and Genomics (ACMG) guideline. In the future, information on novel pathogenic variants, obtained from study-based genetic testing, will be added as items to the social health insurance-based screening, and is expected to be beneficial for patients with hearing loss.
We present the support system for hearing impairment infants and young children with multiple disabilities provided at the Hiroshima City Child Care and Guidance Center. The subjects were 39 cases with multiple disabilities diagnosed as having hearing impairment seen at our center between April 2012 and March 2017. Three types of support were provided to the subjects enrolled in this study. The first type was provided to 14 cases with “severe mental retardation and motor disability.” We enrolled them at both the “Department of audiological habilitation for multiple disabilities” and “Daycare institution for intellectual and/or motor disabilities,” and coordinated the care given at both institutions. The second type was used for 9 cases with “moderate mental retardation” at the “Daycare institution for hearing-impaired children.” We adjusted the habilitation programs according to the level of development and degree of disabilities. The third type was provided to 16 cases with “Autism Spectrum Disorder (ASD).” We adopted “Autism treatment techniques” for these patients at the daycare institution.
For all types, cooperation among the facilities and habilitation based on the disabity characteristics may promote their development. Furthermore, improvement of the third type, because delay in its start might have strengthened the ASD characteristics, and some problems were identified in the way the parents took notice of the symptoms before ASD diagnosis.
New insights from animal studies suggest that the most vulnerable elements in the inner ear are the synaptic connections between the inner hair cells and the cochlear neurons. We show a case with a normal pure-tone audiogram, poor word recognition score, and reduction of the ABR amplitude, suggesting the validity of measuring cochlear synaptopathy. ABR wave I is useful in animal models. However, the amplitude of ABR wave I shows both high inter-subject and intra-subject variability in humans, so that its clinical usefulness is restricted. In this study, the intra-subject variability of the ABR amplitude was investigated. The variance of the background noise was practically negligible, allowing estimation of the variance of the evoked potential recorded in response to stimulus levels of over 40dB nHL. In a normal-hearing subject, the standard deviation of the wave I amplitude tended to decrease as the sample size increased from 500 to 2000 repetitions. Assuming that the 40dB nHL for normal hearing was equivalent to the threshold for hearing loss of 30dB SL, the wave I amplitude in ears with hearing loss was significantly higher than that in ears with normal hearing. The coefficient of variation (CV) of the wave I amplitude in ears with hearing loss was significantly smaller than that in ears with normal hearing.
Tinnitus, hearing loss, and depression have all been reported as symptoms of zinc deficiency. However, few studies have examined the association of all these three symptoms developing at the same time. Thus, we studied the association between serum zinc level and tinnitus, hearing loss, depression in community-dwelling middle-aged and elderly Japanese subjects. The subjects of this study were 734 men and 695 women who participated in both the 2nd wave and 4th wave of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). Multiple logistic regression analysis with adjustments for the age, sex, tinnitus, hearing loss, depression, history of noise exposure, history of ear disease, low income, smoking habits, and alcohol intake of the baseline revealed that zinc deficiency at the baseline (2nd wave) was significantly associated with the development of depressive symptoms 4 years later (odds ratio 1.66, p=0.025), but not with that of tinnitus, tinnitus annoyance or hearing loss 4 years later. Our results confirmed previous suggestions that zinc deficiency is a significant risk factor for depression, and suggested that the serum zinc levels should be checked in patients with tinnitus and depression.
(Background) Diagnosis and treatment of tinnitus would benefit from identification of neural correlates of tinnitus perception in the central nervous system. Here, we hypothesized that tinnitus perception could be predicted from neural synchrony of spontaneous activities in the auditory cortex, because sustained tones induced auditory cortical synchrony.
(Method) Eight Wistar rats were overexposed in their left ear to a pure tone (10kHz, 125dB SPL) for 1h. Before and 2-8 days after the exposure, pre-pulse and gap inhibition tests were performed for examination of the behavioral signs of hearing loss and tinnitus. Local field potentials (LFP) of spontaneous activities in layer IV of the right auditory cortex were investigated using a microelectrode array with 96 recording sites under anesthesia. Band-specific phase locking value (PLVs) between LFPs at each site quantified the neural synchrony.
(Results) The exposed group exhibited behavioral signs of tinnitus around 32kHz. For the theta (4-8Hz) and alpha (8-14Hz) bands, the PLV between the 10kHz and 22-45kHz tonotopic regions was significantly higher in the exposed group than in the control group. This synchrony was positively correlated with the tinnitus scores.
(Conclusion) Synchrony of spontaneous activities in the auditory cortex may offer prospective insights into diagnostic and therapeutic developments for tinnitus.