Major Cause Of Deafness Research Articles

Cochlear Implantation in Adults with Post-lingual Hearing Loss: Clinico-Demographical Study and Outcomes in the Current Times.

To describe clinico-demographical profile for post-lingual hearing loss in the adults undergoing cochlear implantation and their outcomes. A retrospective chart review was conducted including adult patients (> 18 years) with bilateral post-lingual severe to profound hearing loss who underwent cochlear implantation in a tertiary care hospital of north India. The clinico-demographical details were collected and the outcomes of the procedure were assessed in terms of speech intelligibility scores, usage and satisfaction scores. Twenty-one patients were included with a mean age of 38.6 years with 15 males and 6 females. The major cause of deafness was infections followed by ototoxicity. The complication rate was 4.8%. Preoperative SDS was not recordable in any of the patients. The mean postoperative SDS was 74%, with no issue of device malfunction in a mean follow-up of 44 months. Cochlear implantation is a safe surgery with good outcomes in post-lingually deafened adults with the major cause for deafness being infections.

AAV-Net1 facilitates the trans-differentiation of supporting cells into hair cells in the murine cochlea.

Mechanosensitive hair cells (HCs) in the cochlear sensory epithelium are critical for sound detection and transduction. Mammalian HCs in the cochlea undergo cytogenesis during embryonic development, and irreversible damage to hair cells postnatally is a major cause of deafness. During the development of the organ of Corti, HCs and supporting cells (SCs) originate from the same precursors. In the neonatal cochlea, damage to HCs activates adjacent SCs to act as HC precursors and to differentiate into new HCs. However, the plasticity of SCs to produce new HCs is gradually lost with cochlear development. Here, we delineate an essential role for the guanine nucleotide exchange factor Net1 in SC trans-differentiation into HCs. Net1 overexpression mediated by AAV-ie in SCs promoted cochlear organoid formation and HC differentiation under two and three-dimensional culture conditions. Also, AAV-Net1 enhanced SC proliferation in Lgr5-EGFPCreERT2 mice and HC generation as indicated by lineage tracing of HCs in the cochleae of Lgr5-EGFPCreERT2/Rosa26-tdTomatoloxp/loxp mice. We further found that the up-regulation of Wnt/β-catenin and Notch signaling in AAV-Net1-transduced cochleae might be responsible for the SC proliferation and HC differentiation. Also, Net1 overexpression in SCs enhanced SC proliferation and HC regeneration and survival after HC damage by neomycin. Taken together, our study suggests that Net1 might serve as a potential target for HC regeneration and that AAV-mediated gene regulation may be a promising approach in stem cell-based therapy in hearing restoration.

Noise Mapping, Prevalence and Risk Factors of Noise-Induced Hearing Loss among Workers at Muscat International Airport.

Noise-induced hearing loss (NIHL) is a common occupational hazard and a major cause of deafness among airport workers. However, few studies have been conducted to investigate the various risk factors related to hearing loss. Purpose: the purpose of this study was to measure the prevalence and risk factors of NIHL among Muscat International Airport airside workers. Method: Their daily noise exposure level at the airport was measured, and the time-weighted average (TWA) was calculated for each airside department. A cross-sectional study design involving 312 workers from the eight departments of the airport was chosen and the prevalence of NIHL among workers was assessed. The study participants then completed a self-administered questionnaire that covered their socio-demographic characteristics, occupational exposure history and the health-related risk factors of NIHL. Results: The TWA recorded for the workers was above the accepted limit in some departments, namely, cabin appearance, ramp, line maintenance and hangar. The prevalence of NIHL among participants was 21.79% (n = 68). Of these 68 participants with NIHL, 22.30% were exposed to job-related high noise levels. NIHL was common among participants aged 40 or above (57.35%, n = 39) and high school degree holders (29.60%, n = 29), as well as those who were exposed to higher noise levels (84.89%, n = 191) or who did not wear their hearing protection devices (HPDs) regularly (53.65%, n = 125). Conclusion: around a quarter of our study participants who were exposed to high noise levels suffer from NIHL.

In vivo CRISPR-Cas9-mediated DNA chop identifies a cochlear outer hair cell-specific enhancer.

Cochlear outer hair cells (OHCs) are essential for hearing. A short, OHC-specific enhancer is necessary but not yet available for gene therapeutic applications in OHC damage. Such damage is a major cause of deafness. Prestin is a motor protein exclusively expressed in OHCs. We hypothesized that the cis-regulatory DNA fragment deletion of Slc26a5 would affect its expression. We tested this hypothesis by conducting CRISPR/Cas9-mediated large DNA fragment deletion of mouse Slc26a5 intron regions. First, starting from a ~13kbp fragment, step-by-step, we narrowed down the sequence to a 1.4kbp segment. By deleting either a 13kbp or 1.4kbp fragment, we observed delayed Prestin expression. Second, we showed that 1.4kbp was an OHC-specific enhancer because enhanced green fluorescent protein (EGFP) was highly and specifically expressed in OHCs in a transgenic mouse where EGFP was driven by the 1.4kbp segment. More importantly, specific EGFP was also driven by its homologous 398bp fragment in human Slc26a5. This suggests that the enhancer is likely to be evolutionarily conserved across different species.

Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges.

Hearing impairment is the most frequent sensory deficit in humans of all age groups, from children (1/500) to the elderly (more than 50% of the over-75 s). Over 50% of congenital deafness are hereditary in nature. The other major causes of deafness, which also may have genetic predisposition, are aging, acoustic trauma, ototoxic drugs such as aminoglycosides, and noise exposure. Over the last two decades, the study of inherited deafness forms and related animal models has been instrumental in deciphering the molecular, cellular, and physiological mechanisms of disease. However, there is still no curative treatment for sensorineural deafness. Hearing loss is currently palliated by rehabilitation methods: conventional hearing aids, and for more severe forms, cochlear implants. Efforts are continuing to improve these devices to help users to understand speech in noisy environments and to appreciate music. However, neither approach can mediate a full recovery of hearing sensitivity and/or restoration of the native inner ear sensory epithelia. New therapeutic approaches based on gene transfer and gene editing tools are being developed in animal models. In this review, we focus on the successful restoration of auditory and vestibular functions in certain inner ear conditions, paving the way for future clinical applications.

Identification of six novel variants in Waardenburg syndrome type II by next-generation sequencing.

BackgroundWaardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous auditory‐pigmentary syndrome characterized by nonprogressive sensorineural hearing loss and iris discoloration. This study aimed to investigate the underlying molecular pathology in Chinese WS families.MethodsA total of 13 patients with Waardenburg syndrome type II (WS2) from six unrelated Chinese families were enrolled. We investigated the mutation profile of genes related to congenital deafness in these families through a targeted sequencing technology and validated the candidate variants by Sanger sequencing.ResultsWe identified six novel variants in microphthalmia‐associated transcription factor (MITF) and SRY‐box 10 (SOX10), which were predicted to be disease causing by in silico analysis. Our results showed that mutations in SOX10 and MITF are two major causes of deafness associated with WS, and de novo mutations were frequently found in probands with SOX10 mutations but not in those with MITF mutations.ConclusionResults showed that targeted next‐generation sequencing (NGS) enabled us to detect disease‐causing mutations with high accuracy, stability, speed and throughput. Our study extends the pathogenic mutation spectrum of MITF and SOX10.

Healthy lifestyle consultation based on traditional Chinese medicine versus routine patient education in the treatment of idiopathic sudden sensorineural hearing loss after failure of systemic therapy: study protocol for a clinical randomised trial

BackgroundIdiopathic sudden sensorineural hearing loss (ISSNHL) is a major cause of deafness. Despite the advances in systemic therapy, some cases of ISSNHL are untreated, because the exact ISSNHL aetiology is unclear. Traditional Chinese medicine (TCM) has been used to treat diseases for thousands of years and is popular and widely practiced in Asia. TCM includes guidance on a healthy lifestyle. In recent decades, the relationship between lifestyle and disease has been emphasised; an unhealthy lifestyle may lead to illnesses. Thus, this study aims to compare the efficacy of lifestyle modification based on TCM with the usual consultation of ISSNHL after failure of a 2-week systemic therapy to provide a scientific basis for clinical decisions.MethodsThis study is a clinical randomised trial that involves 56 patients diagnosed with ISSNHL but who have had incomplete recovery after initial management (at least 2 weeks of routine Western medical treatment). The study is performed in accordance with the sudden hearing loss clinical guideline of the American Academy of Otolaryngology–Head and Neck Surgery, published in 2012. Participants are randomly distributed into two groups: the healthy lifestyle modification group based on TCM and the control group (1:1 ratio). Patient follow-up lasts for 3 months. The primary outcome measure is the effective rate of hearing improvement, which is defined as the proportion of patients with at least 15 dB of improvement in the average thresholds of hearing loss frequency. The secondary outcome measures are improvements in word recognition score, Tinnitus Handicap Inventory and visual analogue scale for ear blockage and dizziness. Assessments are made at baseline and after lifestyle modification for 1 and 3 months.DiscussionThe efficacy of healthy lifestyle modification based on a TCM programme for patients with ISSNHL with incomplete recovery after failure of initial systemic therapy is determined in this trial. Positive results will provide clinical evidence on the effects of a TCM-based healthy lifestyle, which could be recommended as salvage therapy for patients with ISSNHL.Trial registrationChinese Clinical Trial Registry, ChiCTR-INR-17011459. Registered on 22 May 2017.

Merits and demerits of transcanal tympanoplasty: an observational study

<p class="abstract"><strong>Background:</strong> Chronic suppurative otitis media characterized by ear discharge, membrane perforation and hearing impairment is a major cause of deafness in India. Tympanoplasty with or without mastoidectomy done by postaural, endaural or transcanal approach is the treatment. Each approach has its advantages and limitations. The transcanal approach is becoming more popular today. A detailed study on the merits and demerits of the transcanal approach to tympanoplasty could not be found in the literature. This study compares this with the postaural approach. The study is aimed to evaluate the merits and demerits of transcanal tympanoplasty.</p><p class="abstract"><strong>Methods:</strong> This study comparing transcanal versus postaural approach in tympanoplasty was carried out between April 2014 and April 2015 for 12 months. A total of 50 patients were divided into two groups (25 each in a group) and compared 11 parameters.</p><p class="abstract"><strong>Results:</strong> Out of 11 parameters, 5 showed a statistically significant difference between the two, favouring transcanal approach. However, surgical results were similar.</p><p><strong>Conclusions:</strong> Transcanal approach has more merits and fewer demerits than others for tympanoplasty, with equal hearing results.</p>

Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea

BackgroundInner ear hair cells as mechanoreceptors are extremely important for hearing. Defects in hair cells are a major cause of deafness. Induced pluripotent stem cells (iPSCs) are promising for regenerating inner ear hair cells and treating hearing loss. Here, we investigated migration, differentiation, and synaptic connections of transplanted otic epithelial progenitors (OEPs) derived from human iPSCs in mouse cochlea.MethodsHuman urinary cells isolated from a healthy donor were reprogramed to form iPSCs that were induced to differentiate into OEPs and hair cell-like cells. Immunocytochemistry, electrophysiological examination, and scanning electron microscopy were used to examine characteristics of induced hair cell-like cells. OEP-derived hair cell-like cells were cocultured with spiral ganglion neurons (SGNs), and the markers of synaptic connections were detected using immunocytochemistry and transmission electron microscope. In vivo, OEPs derived from iPSCs were transplanted into the cochlea of mice by injection through the round window. Migration, differentiation, and synaptic connections of transplanted cells were also examined by thin cochlear sectioning and immunohistochemistry.ResultsThe induced hair cell-like cells displayed typical morphological characteristics and electrophysiological properties specific to inner hair cells. In vitro, OEP-derived hair cell-like cells formed synaptic connections with SGNs in coculture. In vivo, some of the transplanted cells migrated to the site of the resident hair cells in the organ of Corti, differentiated into hair cell-like cells, and formed synaptic connections with native SGNs.ConclusionsWe conclude that the transplantation of OEPs is feasible for the regeneration of hair cells. These results present a substantial reference for a cell-based therapy for the loss of hair cells.

Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia

BackgroundMutations in GJB2 gene are a major causes of deafness and their spectrum and prevalence are specific for various populations. The well-known mutation c.35delG is more frequent in populations of Caucasian origin. Data on the c.35delG prevalence in Russia are mainly restricted to the European part of this country. We aimed to estimate the carrier frequency of c.35delG in Western Siberia and thereby update current data on the c.35delG prevalence in Russia. According to a generally accepted hypothesis, c.35delG originated from a common ancestor in the Middle East or the Mediterranean ~ 10,000–14,000 years ago and spread throughout Europe with Neolithic migrations. To test the c.35delG common origin hypothesis, we have reconstructed haplotypes bearing c.35delG and evaluated the approximate age of c.35delG in Siberia.MethodsThe carrier frequency of c.35delG was estimated in 122 unrelated hearing individuals living in Western Siberia. For reconstruction of haplotypes bearing c.35delG, polymorphic D13S141, D13S175, D13S1853 flanking the GJB2 gene, and intragenic rs3751385 were genotyped in deaf patients homozygous for c.35delG (n = 24) and in unrelated healthy individuals negative for c.35delG (n = 67) living in Siberia.ResultsWe present updated carrier rates for c.35delG in Russia complemented by new data on c.35delG carrier frequency in Russians living in Western Siberia (4.1%). Two common D13S141-c.35delG-D13S175-D13S1853 haplotypes, 126-c.35delG-105-202 and 124-c.35delG-105-202, were reconstructed in the c.35delG homozygotes from Siberia. Moreover, identical allelic composition of the two most frequent c.35delG haplotypes restricted by D13S141 and D13S175 was established in geographically remote regions: Siberia and Volga-Ural region (Russia) and Belarus (Eastern Europe).ConclusionsDistribution of the c.35delG carrier frequency in Russia is characterized by pronounced ethno-geographic specificity with a downward trend from west to east. Comparative analysis of the c.35delG haplotypes supports a common origin of c.35delG in some regions of Russia (Volga-Ural region and Siberia) and in Eastern Europe (Belarus). A rough estimation of the c.35delG age in Siberia (about 4800 to 8100 years ago) probably reflects the early formation stages of the modern European population (including the European part of the contemporary territory of Russia) since the settlement of Siberia by Russians started only at the end of sixteenth century.

Barhl1 is required for the differentiation of inner ear hair cell-like cells from mouse embryonic stem cells.

Inner ear hair cells are mechanoreceptors responsible for hearing. Pathogenic defects of hair cell-specific genes are one of the major causes of deafness. The BarH class homeobox gene Barhl1 is a deafness gene expressed in developing hair cells, yet the role of Barhl1 during hair cell development remains poorly understood. In the present study, we first established an in vitro differentiation system to efficiently obtain mouse embryonic stem cell (mESC)-derived hair cell-like cells. Subsequently, a mESC line carrying a targeted disruption of Barhl1 was generated using CRISPR/Cas9 technology and subjected to the established in vitro hair cell differentiation protocol. Targeted disruption of Barhl1 does not affect the induction of mESCs toward early primitive ectoderm-like (EPL) cells and otic progenitors but strongly inhibits the differentiation of hair cell-like cells. Using RNA-sequencing and bioinformatics, we further unravel the molecular mechanism underlying Barhl1-mediated hair cell development. Our data demonstrate the essential role of Barhl1 during hair cell development and provide a basis for the treatment of Barhl1 mutation-based deafness.

Diphtheria Toxin-Induced Cell Death Triggers Wnt-Dependent Hair Cell Regeneration in Neonatal Mice.

Cochlear hair cells (HCs), the sensory cells that respond to sound, do not regenerate after damage in adult mammals, and their loss is a major cause of deafness. Here we show that HC regeneration in newborn mouse ears occurred spontaneously when the original cells were ablated by treatment with diphtheria toxin (DT) in ears that had been engineered to overexpress the DT receptor, but was not detectable when HCs were ablated in vivo by the aminoglycoside antibiotic neomycin. A variety of Wnts (Wnt1, Wnt2, Wnt2b, Wnt4, Wnt5a, Wnt7b, Wnt9a, Wnt9b, and Wnt11) and Wnt pathway component Krm2 were upregulated after DT damage. Nuclear β-catenin was upregulated in HCs and supporting cells of the DT-damaged cochlea. Pharmacological inhibition of Wnt decreased spontaneous regeneration, confirming a role of Wnt signaling in HC regeneration. Inhibition of Notch signaling further potentiated supporting cell proliferation and HC differentiation that occurred spontaneously. The absence of new HCs in the neomycin ears was correlated to less robust Wnt pathway activation, but the ears subjected to neomycin treatment nonetheless showed increased cell division and HC differentiation after subsequent forced upregulation of β-catenin. These studies suggest, first, that Wnt signaling plays a key role in regeneration, and, second, that the outcome of a regenerative response to damage in the newborn cochlea is determined by reaching a threshold level of Wnt signaling rather than its complete absence or presence. Sensory HCs of the inner ear do not regenerate in the adult, and their loss is a major cause of deafness. We found that HCs regenerated spontaneously in the newborn mouse after diphtheria toxin (DT)-induced, but not neomycin-induced, HC death. Regeneration depended on activation of Wnt signaling, and regeneration in DT-treated ears correlated to a higher level of Wnt activation than occurred in nonregenerating neomycin-treated ears. This is significant because insufficient regeneration caused by a failure to reach a threshold level of signaling, if true in the adult, has the potential to be exploited for development of clinical approaches for the treatment of deafness caused by HC loss.

Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation.

Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.

The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations.

Deafness encompasses a series of etiologically heterogeneous disorders with mutations in more than 400 independent genes. However, several studies indicate that a large proportion of both syndromic and nonsyndromic forms of deafness in the racially diverse Indian and Pakistani populations are caused by defects in just a few genes. In these countries, there is a strong cultural preference for consanguineous marriage and an associated relatively high prevalence of genetic disorders. The current Indian population is approximately 1.2 billion and it is estimated that 30,000 infants are born with congenital sensorineural hearing loss (HL) each year. The estimated rate of profound bilateral HL is 1.6 per 1000 in Pakistan and 70% of this HL arises in consanguineous families. Knowledge of the genetic cause of deafness within a distinct population is important for accurate genetic counseling and early diagnosis for timely intervention and treatment options. Many sources and technologies are now available for the testing of hearing efficiency. Population-based screening has been proposed as one of the major strategies for translating genetic and genomic advances into population health gains. This review of the genetics of deafness in Indian and Pakistani populations deals with the major causes of deafness in these countries and prospectives for reducing the incidence of inherited deafness.

Effect of Growth Factor Supplementation on the Hair Cell Specific Markers of Cells Harvested from Basilar Membrane.

Loss of auditory hair cells is a major cause of deafness. The presence of auditory progenitor cells in the inner ear raises the hope for mammalian inner ear cell regeneration. In this study, we aimed to investigate the effect of growth factor supplementations, namely a combination of epidermal growth factor (EGF), insulin-like growth factor (IGF), and beta (β)-fibroblast growth factor (βFGF), on the expression of hair cell-specific markers by cells harvested from the cochlear membrane. This would provide an insight into the capability of these cells to differentiate into hair cells. EGF, IGF, and βFGF were supplemented into the culture medium. The cells were evaluated by morphology, growth kinetic, gene expression, and protein expression. The cultured cells of mouse basilar membrane were spindle shaped. Growth factors-enriched medium promotes a significantly higher proliferative activity than the basic culture medium but did not alter the cell morphology. Growth factors-enriched medium did not show any significant differences in the protein expression of the hair cell-specific markers myosin VIIa and calretinin and the stem-cell marker nestin. Gene expression analysis showed that the expression of the hair cell-specific genes myosin VIIa and calretinin as well as the stem cell genes nestin, Rex1, and Sox2 was reduced after the cells were passaged in the growth factor-supplemented medium. Cells in the basic medium expressed a significantly higher level of hair cell-specific genes at certain passages. Growth factor supplementation could not maintain the expression of hair cell-specific markers by cells obtained from the cochlear membrane.

Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors

Mammalian hair cells do not regenerate, and their loss is a major cause of deafness. We recently identified leucine-rich repeat containing, G-protein-coupled receptor 5 (Lgr5)-expressing cochlear supporting cells with the capacity for self-renewal and hair cell differentiation in vitro. We found that these cells, a subset of cochlear supporting cells, were responsive to Wnt signaling. Here we asked whether these Lgr5-positive cells, despite their lack of contribution to hair cell replacement after degenerative loss, could be driven by forced expression of β-catenin to act as hair cell progenitors in vivo. We showed that forced stabilization of β-catenin in supporting cells in neonatal animals resulted in proliferation of supporting cells and generation of hair cells. Although β-catenin expression was increased by genetic means in all supporting cells, entry to the cell cycle and differentiation to hair cells of the normally postmitotic cells was restricted to the Lgr5-positive population. Our finding suggests that Wnt/β-catenin can drive Lgr5-positive cells to act as hair cell progenitors, even after their exit from the cell cycle and apparent establishment of cell fate.

Genetic Screening ofGJB2andSLC26A4in Korean Cochlear Implantees: Experience of Soree Ear Clinic

ObjectivesGenetic hearing loss is highly heterogeneous and more than 100 genes are predicted to cause this disorder in humans. In spite of this large genetic heterogeneity, mutations in SLC26A4 and GJB2 genes are primarily responsible for the major etiologies of genetic hearing loss among Koreans. The purpose of this study is to investigate the genetic cause of deafness in Korean cochlear implantees by performing a genetic screening of the SLC26A4 and GJB2 genes.MethodsThe study cohort included 421 unrelated Korean patients with sensorineural hearing loss (SNHL) and who had received cochlear implants (CI) at Soree Ear Clinic from July 2002 to December 2010. Among 421 CI patients, we studied 230 cases who had received the genetic screening for SLC26A4 or GJB2 genes. Written informed consent was obtained from all participants. All patients had severe to profound, bilateral hearing loss. For 56 patients who showed enlarged vestibular aqueduct on their computed tomography (CT) scan, we analyzed SLC26A4. For 174 CT negative patients, GJB2 gene was sequenced.ResultsFor the 56 SLC26A4 patients, 32 (57.1%) had two pathogenic recessive mutations in SLC26A4. A single recessive SLC26A4 mutation was identified in 14 patients (25%). H723R and IVS7-2A>G were the most commonly found mutations, accounting for 60.3% (47/78) and 30.8% (24/78) of the mutated alleles, respectively. For the 174 GJB2 patients, 20 patients (11.5%) had two pathogenic recessive mutations in GJB2. 235delC was the most common mutation, accounting for 43.0% (31/72) of mutant alleles.ConclusionThe two major genes, SLC26A4 and GJB2, contribute major causes of deafness in CI patients. Continuous studies are needed to identify new genes that can cause hearing loss to Korean CI patients.

High Prevalence of the Connexin 26 (GJB2) Mutation in Chinese Cochlear Implant Recipients

Background: The GJB2 gene, mapping to chromosome 13q12, encodes a gap junction protein, connexin 26, and is responsible for certain forms of congenital deafness, such as DFNB1 and DFNA3. Mutations of this gene are responsible for about one half of severe autosomal recessive non-syndromic deafness. Methods: To determine whether GJB2 mutations are major causes of deafness in Chinese cochlear implant recipients, we enrolled 115 cochlear implant recipients for mutation screening. Results: The results showed that 36.5% (42/115) of all cochlear implant recipients and 41% (41/100) of non-syndromic deafness patients exhibit GJB2 mutations; only 1 inner ear malformation patient was detected with GJB2 mutations. The present study found 11 different variations in the GJB2 gene. Conclusion: The 235delC mutation was the most prevalent mutation, found in 18.3% (42/230 alleles) of all cochlear implant recipients and 21.0% (42/200 alleles) of the non-syndromic deafness group. Only 0.6% of GJB2 mutations were detected in the inner ear malformation group. The novel 187G→T mutations are likely to be pathological mutations.

Genetic analysis of family constellation for cochlear implant

GJB2, SLC26A4 (PDS) and mitochondrial DNA (mtDNA) have been associated with sensorineural hearing loss. In the present study, the clinical, genetic and molecular analysis of 14 cochlear implant recipients and their parents was studied from April 2006 to September 2007. Of the 14 subjects, 35.7% had gene mutations; 28.6% had homozygous GJB2 235delC mutation, whose parents carried heterozygous GJB2 235delC mutation; and 7.1% had mtDNA A1555G mutation, whose mother carried mtDNA A1555G mutation too. There was no SLC26A4 (PDS) mutation. These results strongly suggested that the mutation in GJB2 gene was a major cause of deafness in cochlear implant recipients and the mutation of mtDNA A1555G was another important cause. Genetic test of hot-spots and analysis of family constellation can offer an accurate genetic counseling to deaf family and reduce the incidence of hearing loss.

Cochlear Stem Cells/Progenitors and Degenerative Hearing Disorders

Hearing loss (deafness) affects approximately 250 million people globally. The major cause of deafness is loss of hair cells and spiral ganglion neurons due to aging, antibiotic use, noise exposure, and genetic defects. At the present time, there is no effective method for restoration of hearing biologically. Cochlear stem cells/progenitors (CSCs), quiescent in the organ of Corti, are excellent candidates for restoration of cell types in the organ of Corti biologically. However, little is known about the biology of CSCs and developmental cues for CSCs to differentiate into hair cells and neurons at the present time. In this article, we briefly reviewed the isolation of CSCs from the postnatal organ of Corti in mice and their capability to differentiate into hair cells and neurons in vitro under the guidance of a group of growth factors: sonic hedgehog (SHH), epidermal growth factor (EGF), retinoic acid (RA), and brain-derived neurotrophic factor (BDNF), herein termed SERB. The identification of CSCs and their differentiation signals is potentially of clinical importance.