APPLICATION OF GENETIC DEAFNESS GENE CHIP FOR DETECTION OF GENE MUTATION OF DEAFNESS IN PREGNANT WOMEN

Objective The study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. Methods The pregnant women in obstetric clinic without hearing impairment and hearing disorders family history were selected. The informed consent was signed. Peripheral blood was taken to extract genom- ic DNA. Application of genetic deafness gene chip for detecting 9 mutational hot spot of the most common 4 Chinese deafness genes, namely GJB2 （35delG, 176del16bp, 235delC, 299delAT）, GJB3 （C538T） ,SLC26A4 （ IVS72A〉G, A2168G） and mito- chondrial DNA 12S rRNA （A1555G, C1494T） . Further genetic testing were provided to the spouses and newborns of the screened carriers. Results Peripheral blood of 430 pregnant women were detected, detection of deafness gene mutation carri- ers in 24 cases（4.2%）, including 13 cases of the GJB2 heterozygous mutation, 3 cases of SLC26A4 heterozygous mutation, 1 cases of GJB3 heterozygous mutation, and 1 case of mitochondrial 12S rRNA mutation. 18 spouses and 17 newborns took further genetic tests, and 6 newborns inherited the mutation from their mother. Conclusion The common deafness genes muta- tion has a high carrier rate in pregnant women group, 235delC and IVS7-2A〉G heterozygous mutations are common.

The effect of right versus left long-term single-sided deafness on sound source localization

Purpose: To analyze the effect of right versus left long-term single-sided deafness(SSD) on sound source localization(SSL), discuss the necessity of intervention and treatment for SSD patients, and analyze the therapeutic effect of long-term unilateral cochlear implantation(UCI) from the perspective of SSL.Methods: This study included 25 patients with SSD, 11 patients with UCI, and 30 participants with normal hearing(NH). Their SSL ability was tested by obtaining their average root mean square(RMS) error values of SSL test.Results: The results showed that the RMS error value of SSD, UCI and NH groups were 52.26 ± 20.25°, 69.84 ±12.14° and 4.27 ± 2.66°, respectively. The ability of SSL was better in the SSD-L group than that in the SSD-R group, and no significant difference existed in the SSD-R and the UCI group.Conclusion: When bilateral deafness patients select unilateral treatment, right-side cochlear implantation may be more beneficial in terms of SSL, which means that the central auditory cortex in long-term SSD patients is affected differently based on which side their deafness occurs.

Electrophysiology and genetic testing in the precision medicine of congenital deafness:A review

Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling.Electrophysiologic techniques such as electrocochleography(ECochG)and electrically-evoked compound action potentials(eCAP)are being studied to localize pathology and estimate residual cochlear vs.neural health.This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing(ECochG and eCAP)are reviewed,and how they complement each other in the diagnostics and prognostication of hearing outcomes.Used together,these measures improve the understanding of insults to the auditory system,allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.Conclusion:Despite tremendous discovery in deafness genes,the effects of individual genes on neural function remain poorly understood.Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice.The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.

The Genetic Deafness in Chinese Population

Deafness is an etiologically heterogeneous trait with many known genetic, environmental causes or a combination thereof. The identification of more than 120 independent genes for deafness has provided profound new insights into the pathophysiology of hearing. However, recent findings indicate that a large proportion of both syndromic and nonsyndromic forms of deafness in Chinese population are caused by a small number of mutations. This review is focused on syndromic and nonsyndromic deafness as well as on the latest information linking inherited mitochondrial pathologies to a variety of etiologies of sensorineural deafness in Chinese population. Better understanding of the genetic causes of deafness in Chinese population is important for accurate genetics counseling and early diagnosis for timely intervention and treatment options.

Cochlear homeostasis and its role in genetic deafness

Each component of the human ear performs a specific function in hearing.The actual process of sound transduction takes place in the auditory portion of the inner ear,the fluid-filled cochlea.In the cochlea,the sensitivity and efficiency of sensory apparatus to convert mechanical energy into neural activity,largely depends on the fluidic and ionic environment.In the lateral wall of cochlea,the secretory epithelium stria vascularis plays an important role in the maintenance of fluidic and ionic homeostasis.A variety of gene mutations disturbs the cochlear homeostasis and subsequently leads to hearing impairment.The review covers several aspects of cochlear homeostasis,from cochlear fluid and the functional role of stria vascularis,cochlear K+ recycling and its molecular substrates to genetic deafness with abnormal cochlear homeostasis.

Prenatal ultrasonography and genetic analysis of fetal cleidocranial dysplasia:A case report

BACKGROUND Cleidocranial dysplasia(CCD)is an infrequent clinical condition with an autosomal dominant inheritance pattern.It is characterized by abnormal clavicles,patent sutures and fontanelles,supernumerary teeth,and short stature.Approximately 60%-70%of patients with CCD have mutations in the RUNX family transcription factor 2 gene.However,prenatal diagnosis of CCD is difficult when the family history is unknown.CASE SUMMARY We report a rare case of fetal CCD with an unknown family history,confirmed by prenatal ultrasonography and genetic testing at a gestational age of 16 weeks.The genetic reports indicated that the fetus carried pathogenic mutations in the RUNX family transcription factor 2 gene(c.674G>A).After careful consideration,the pregnant woman and her family decided to continue the pregnancy.CONCLUSION Definitive prenatal diagnosis of CCD should include family history,ultrasound diagnosis,and genetic analysis,especially if family history is unknown.

HUMAN MITOCHONDRIAL tRNA MUTATIONS IN MATERNALLY INHERITED DEAFNESS

Mutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syn-dromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR) 3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mu-tations including tRNASer(UCN) 7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A are insufficient to produce a deafness phe-notype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochon-drial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deaf-ness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness.

A screening analysis of the GJB2 c.176 del 16 mutation responsible for hereditary deafness in a Chinese family

Objective:To determine whether a new-born child from a family carrying a deafness gene needs cochlear implantation to avoid dysphonia by screening and sequencing a deafness-related gene.Results:Both screening and sequencing results confirmed that the new born child had a normal GJB2 gene despite the fact that she has a brother suffering from hearing loss triggered by an allelic GJB2 c.176 del 16 mutation.We cloned the GJB2 genes derived from their respective blood genomic DNA into GFP fused plasmids and transfected those plasmids into the 293 T cell line to test for gene function.While the mutated GJB2gene(GJB2 c.176 del 16) of her deaf brother was found to be unable to form the gap junction structure between two adjacent cells,the baby girl’s GJB2 gene ran into no such problems.Conclusion:The screening and sequencing as well as the GJB2 gene function tests invariably showed results consistent with the ABR tested hearing phenotype,which means that the child,with a normal wild type GJB2 gene,does not need early intervention to prevent her from developing hearing loss and dysphonia at a later stage in life.

Outcomes of treatment of sudden deafness using different Protocols:a retrospective analysis of 104 cases

Objective To compare different treatment protocols for sudden deafness(SD), for the purpose of identifying an appropriate approach to SD. Methods A total of 104 patients with diagnosis of sudden hearing loss treated from Jan 2006 to December 2008 were included in this study, of which 31 received the typical pharmaceutical treatment (groupⅠ), 40 received the typical pharmaceutical treatment plus polarized liquid (GroupⅡ) and 33 received the hyperbaric oxygen in addition to the treatment included in Group Ⅱ(Group Ⅲ). Results The total improvement rate (67.74%, 62.50% and 75.76% for Groups Ⅰ, Ⅱ and Ⅲ respectively) was not statistically different between the three groups (P > 0.05). Conclusion The three treatment protocols are similar when judged by the treatment outcomes in SD, neither being superior to the others. The two important factors that appear to influence treatment outcomes are the audiogram pattern and duration of hearing loss before seeking treatment. Patients with upsloping or peak-type audiograms and treated within 7 days from the onset have better prognosis than others.

Concurrent symptoms and disease conditions in sudden deafness

Objective To study concomitant symptoms and disease conditions in sudden deafness. Methods Clinical data of 418 cases of sudden deafness treated in this department from 2000 to 2007 were reviewed. Results Of the 418 cases, 201 were males and 217 were females. Right ear was involved in 184 cases and left ear in 191 cases. Bilateral involvement was seen in 43 cases. The average age was 44.1 years. Tinnitus was reported in 369 cases (88.3%) either before or after hearing loss, of which 64.5% was of low pitch, 27.1% of high pitch and 8.4% of mixed tones. Constant tinnitus was reported in 83% of the cases, and muffled feelings in 33.3% of the cases. Hearing loss was the only complaint in 221 cases (52.9%). Dizziness was reported in 77 cases (18.4%) and vertigo attacks in 120 cases (28%). Hypertension, coronary artery disease and diabetes were found in 19.6% of 418 cases and hyperlipidemia in 54.5% of 211 cases. CT and / or MRI data were available in 147 cases, with positive findings in 18 cases (12.3%): 2 with acoustic neuroma (1.36%); 4 with emphraxis in the basal ganglia, cerebellum, temporal lobe or parietal lobe, and 12 with poor pneumatization of ipsior contralateral mastoid cells. Conclusion In this case series of sudden deafness, low-pitch constant tinnitus was a common complaint. Most of the studied cases presented with simple hearing loss. Vertigo attacks were more common than dizziness in this group of patients. The most common concomitant disorder was hyperlipidemia, especially high triglycerides. Imaging studies are important in managing sudden deafness in ruling out acoustic neuroma and other intracranial diseases.

A novel mitochondrial tRNA gene mutation in a chinese family with dilated cardiomyopathy and sensorineural deafness

Objective： To determine whether a mutation of mitochondrial DNA induces familial dilated cardiomyopathy in Chinese families with cardiomyopathy, and analyzed the correlation between the genotype and phenotype. Methods： Affected members in three Chinese families of the familial dilated cardiomyopathy underwent clinical evaluation and DNA analysis. Polymerase chain reaction and direct DNA sequencing were used to screen for mitochondrial DNA mutation. The type of mtDNA variations and clinical situation were analysed on the patients with mitochondrial DNA mutation. Results： The mitochondrial A3434G mutation was identified in one of the three families,the 3434 th nucleotide A was replaced by G, which led to change of amino acid. No mutations were identified in the clinically unaffected members of the family and all members of the other two families. Conclusion： This study indicates that the mitochondrial A3434G mutation maybe related with familial dilated cardiomyopathy and deafness.

Traditional Chinese Medicine Nursing Protocols for Sudden Deafness( Sudden Sensorineural Hearing Loss)

Sudden deafness is one of the commonest acute symptoms in otolaryngology.In recent years,the incidence of sudden deafness is on the rise all over the world,but its etiology is still unclear,and the prognosis is greatly different.Traditional Chinese medicine(TCM)believes that the onset of sudden deafness is related to the liver,gallbladder,heart and triple energizer meridians.This article mainly explored the key points of common syndromes,TCM nursing methods and health guidance of sudden deafness.

An efficient strategy for establishing a model of sensorineural deafness in rats

Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.

Profound deafness and the acquisition of spoken language in children

Profound congenital sensorineural hearing loss(SNHL) is not so infrequent,affecting 1 to 2 of every 1000 newborns in western countries.Nevertheless,universal hearing screening programs have not been widely applied,although such programs are already established for metabolic diseases.The acquisition of spoken language is a time-dependent process,and some form linguistic input should be present before the first 6 mo of life for a child to become linguistically competent.Therefore,profoundly deaf children should be detected early,and referred timely for the process of auditory rehabilitation to be initiated.Hearing assessment methods should reflect the behavioural audiogram in an accurate manner.Additional disabilities also need to be taken into account.Profound congenital SNHL is managed by a multidisciplinary team.Affected infants should be bilaterally fitted with hearing aids,no later than 3 mo after birth.They should be monitored until the first year of age.If they are not progressing linguistically,cochlear implantation can be considered after thorough preoperative assessment.Prelingually deaf children develop significant speech perception and production abilities,and speech intelligibility over time,following cochlear implantation.Age at intervention and oral communication,are the most important determi-nants of outcomes.Realistic parental expectations are also essential.Cochlear implant programs deserve the strong support of community members,professional bodies,and political authorities in order to be successful,and maximize the future earnings of pediatric cochlear implantation for human societies.

The Effect of a High-Frequency-Hearing-Threshold Weighted Value on the Diagnosis of Occupational-Noise-Induced Deafness

Objective: In order to provide a theoretical basis for the revision of the current diagnostic criteria for occupational noise-induced deafness (ONID), we evaluated the degree of ONID by analyzing different high-frequency-hearing- threshold-weighted values (HFTWVs). Methods: A retrospective study was conducted to evaluate the diagnosis of patients with ONID from January 2016 to January 2017 in Guangdong province, China. Based on 3 hearing tests (each interval between the tests was greater than 3 days), the minimum threshold value of each frequency was obtained using the 2007 edition’s diagnostic criteria for ONID. The speech frequency and the HFTWVs were analyzed based on age, noise exposure, and diagnostic classi-fication using SPSS21.0. Results: 168 patients in total were involved in this study, 154 males and 14 females, and the average age was 41.18 ± 6.07. The diagnosis rate was increased by the weighted value of the high frequencies and was more than the mean value of the pure speech frequency (MVPSF). The diagnosis rate for the weighted 4 kHz frequency level increased by 13.69% (χ2 = 9.880, P = 0.002), the weighted 6 kHz level increased by 15.47% (χ2 = 9.985, P = 0.002), and the weighted 4 kHz + 6 kHz level increased by 15.47% (χ2 = 9.985, P = 0.002). The differences were all statistically significant. The diagnostic rate of the different thresholds showed no obvious difference between the genders. The age groups were divided into less than or equal to 40 years old (group A) and 40 - 50 years old (group B). There were several groups with a high frequency: high frequency weighted 4 kHz ( group A χ2 = 3.380, P = 0.050;group B χ2 = 4.054, P = 0.032), high frequency weighted 6 kHz (group A χ2 = 6.362, P = 0.012;group B χ2 = 4.054, P = 0.032), weighted 4 kHz + 6 kHz (group A χ2 = 6.362 P = 0.012;B χ2 = 4.054, P = 0.032) than those of MVPSF in the same group on ONID diagnosis rate. The differences between the groups were statistically significant. There was no significant difference between the age groups (χ2 = 2.265, P = 0.944). The better ear’s (the smaller hearing threshold weighted value) MVPSF and the weighted values for the different high frequencies were examined in light of the number of working years;the group that was exposed to noise for more than 10 years had significantly higher values than those of the average thresholds of each frequency band in the groups with 3 - 5 years of exposure (F = 2.271, P = 0.001) and 6 - 10 years of exposure (F = 1.563, P = 0.046). The differences were statistically significant. The different HFTWVs were higher than those of the MVPSF values, and the high frequency weighted 4 kHz + 6 kHz level showed the greatest difference, with an average increase of 2.83 dB. The diagnostic rate that included the weighted high frequency values was higher for the mild, moderate, and severe cases than those patients who were only screened with the pure frequency tests. The results of the comparisons of the diagnosis rates for mild ONID were as follows: the weighted 3 kHz high frequency level (χ2 = 3.117, P = 0.077) had no significant difference, but the weighted 4 kHz level (χ2 = 10.835, P = 0.001), 6 kHz level (χ2 = 9.985, P = 0.002), 3 kHz + 4 kHz level (χ2 = 6.315, P = 0.012), 3 kHz + 6 kHz level (χ2 = 6.315, P = 0.012), 4 kHz + 6 kHz level (χ2 = 9.985, P = 0.002), and 3 kHz + 4 kHz + 6 kHz level (χ2 = 7.667, P = 0.002) were significantly higher than the diagnosis rate of the mean value of the PSF. There was no significant difference between the 2 groups for the moderate and severe grades (P > 0.05). Conclusion: Different HFTWVs increase the diagnostic rate of ONID. The weighted 4 kHz, 6 kHz, and 4 kHz + 6 kHz high frequency values greatly affected the diagnostic results, and the weighted 4 kHz + 6 kHz high frequency hearing threshold value has the maximum the effect on the ONID diagnosis results.

Sudden deafness as a prodrome of cerebellar artery infarction:Three case reports

BACKGROUND To summarize the clinical characteristics of acute cerebral infarction(ACI)in patients with sudden deafness(SD)as the first symptom,improve the awareness of the disease,and help diagnosis and treatment.CASE SUMMARY From 2019 to 2020,three patients with ACI with SD as the first symptom were admitted to our hospital.Pure tone audiometry,head magnetic resonance imaging(MRI),vertebral artery and carotid artery B-ultrasound,head and neck computed tomography angiography,and other examinations were performed.Following the treatment of SD,hearing and dizziness were not significantly improved.Then,the patients developed symptoms of related cranial nerve injury,and brain MRI showed cerebral infarction in the cerebellopontine angle area.All three cases were transferred to the neurology department for relevant conservative treatment.CONCLUSION Patients with ACI with SD as the first symptom usually attend the otolaryngology clinic.Here a diagnosis of SD,which is based on an audiological examination,is made and the corresponding treatment is administered.To reduce the misdiagnosis of this disease,close attention should be paid to the changes in the patient's clinical symptoms and related auxiliary examinations should be performed,such as brain MRI and cerebrovascular imaging.Otolaryngologists should pay attention to the type and severity of hearing loss,the accompanying symptoms,age,high-risk factors for cerebral infarction,and related cranial nerve symptoms in patients with SD.If the patient's early brain MRI does not show abnormalities,monitoring remains essential.The head MRI should be analyzed quickly based on the changes in the symptoms of the patient,to make an accurate diagnosis and provide the timely and correct treatment for the patients.

Child Deafness in Sub-Saharan Africa: Experience of Two ENT Services in Casamance, South of Senegal

Introduction: Hearing impairment is the most common sensory deficit at birth. It is a public health problem because of the repercussions on the communication development, on the education and subsequent social integration of the child. The objective of this study was to determine the epidemiological, clinical, audiometric and etiological profiles of child deafness in Casamance, South of Senegal. Materials and Methods: This was a retrospective multicenter study, which extended a period of 7 years from January 1st, 2012 to December 31st, 2019. All children aged between 1 to 18 years old and received during their first ENT consultations at the regional and PEACE hospital in Ziguinchor were included. Results: One hundred and seventy-eight records of children were collected during this period, that is a prevalence of 1.30%. The average age was 9 years old. Conductive hearing loss was found in 68% of patients, followed by reception hearing deafness in 24%. The deafness was acquired in the majority of cases (93%) and the predominant etiology was infectious. However, the cause was unknown in 7.51% of cases. Conclusion: Child deafness is common in Casamance and is most often underdiagnosed. The acquired forms are the most common, hence the importance of early detection after a rigorous family investigation.

Audiometric Profile of Deafness at the University Hospital Center Gabriel Toure of Bamako

Objective: To determine the audiometric profile of deafness in our practice. Materials and Methods: Longitudinal prospective study was conducted out in the ENT department and cervicofacial surgery of Gabriel Toure University Hospital in Bamako, we made an exhaustive sampling of all the patients who consulted for hearing loss, tinnitus, vertigo, hiring report, medical expertise and whose deafness was confirmed to tonal audiometry with an age greater than or equal to 15 years. It was spread over 10 months (June 2016 to March 2017). A total of 200 patients were collected. Exclusion criteria were all patients under 15 years of age as well as deafness related to earwax or foreign bodies, and refusal to participate in the study Results: During our study period, 6055 outpatients were admitted out of which 734 patients underwent audiometric testing and 200 patients (3.30%) met our criteria. The male sex was the most represented with a rate of 60%. The sex ratio was 1.5 or 3 men for 2 women. The 15 to 25 age group was the most represented at 37.5%. The average age was 37.18 years old with extremes ranging from 15 to 83 years old. Pupils/students were the most represented with a rate of 29.5%, followed by housewives in 23%, farmers in 10.5% and military in 10%. As antecedent 26% of our patients had a chronic otitis media (OMC), against 23% who had no antecedent otological and 17% had a traumatic antecedent. Bilateral deafness was the most common with a rate of 64.5%. The mode of progressive appearance was the most frequent in 74.5%. As functional signs 46.22% of our patients had a hearing loss associated with tinnitus. Otoscopic examination was pathological in 34.5% of our patients. Mixed deafness was the most common in 43.35%, followed by perception deafness in 32.19% and transmission deafness 24.46%. Mean deafness was the most common with a rate of 48.91%, was severe in 20.22%, mild in 18.31%, deep in 11.47% and cophotic in 01.09%. Asymmetrical curves were the most found in 65.89% of our patients. Conclusion: Deafness is a sensory disability responsible for communication disorder, sometimes disabling. Audiometry, although subjective, remains essential in the diagnosis of deafness.

Fine Mapping of a Deafness Mutation hml on Mouse Chromosome 10

Objective To map a mouse deafness gene, identify the underlying mutation and develop a mouse model for human deafness. Methods Genetic linkage cross and genome scan were used to map a novel mutation named hypoplasia of the membranous labyrinth (hml), which causes hearing loss in mutant mice. Results ① hml was mapped on mouse Chr 10 (～43 cM from the centromere) suggests that the homologous human gene is on 12q22-q24, which was defined on the basis of known mouse-human homologies (OMIM, 2004). ② This study has generated 25 polymorphic microsatellite markers, placed 3 known human genes in the correct order in a high-resolution mouse map and narrowed the hml candidate gene region to a 500 kb area.