Severe Sensorineural Deafness Research Articles

Analysis of TRIOBP gene in non-syndromic deafness: A case report.

Through family investigation, the genetic map was drawn and audiological characteristics were analyzed. High-throughput sequencing was used to screen the deafness genes of the proband. Sanger sequencing was used to verify the suspected pathogenic sites in the family. Identify the causes of hearing loss and treatment options. Bilateral moderate to severe sensorineural deafness. After completing the examination, the patient was recommended to wear a hearing aid or do a cochlear implant, but the patient was not treated for personal reasons. All 8 patients in this family were nonsyndromic deafness. The proband had a compound heterozygous mutation of c.A4484T/c.A4510G in the TRIOBP gene, and the patient II-6 had a heterozygous mutation of c.A4484T in the TRIOBP gene. A complex heterozygous mutation of TRIOBP gene c.A4510G/c.G59T was found in II-7, but no reports of pathogenicity of these mutations were found in relevant literatures and databases. In addition, patients II-6, III-4, and III-6 had heterozygous mutations of CHD7 gene c.T2615C and C.3202-5T >C, and patients II-6 and III-4 also had heterozygous mutations of CHD23 gene c.G5312A and c.C6250T. In this study, a new locus of the TRIOBP gene was found, which enriched the gene mutant spectrum and clarified the pathogenic gene of the proband. However, the etiology of deafness in other members of the family needs to be further analyzed.

Comprehensive diagnosis and genetic analysis of two children with ring chromosome 18

To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes. Two patients treated at the Children's Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.21q22.1)[40]/46,XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11-21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them. Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

Hearing loss in children with congenital heart disease

Background : Congenital heart disease (CHD) is a dangerous disease, about 50% of deaths will occur in the first month of life. In developed countries almost all types of congenital heart disease have been detected in infancy even at less than 1 month of age, whereas in developing countries many are only detected after the child is older, so in some severe CHD types may have died before being detected. Rubella infection in pregnancy or congenital rubella syndrome (CRS) can cause miscarriage, fetal death, or congenital abnormalities after birth. CRS is characterized by sensorineural hearing loss (SNHL), congenital cataracts or glaucoma, congenital heart disease, and developmental delays. Purpose : This case report was submitted in order to find out how to properly treat patients with hearing loss with sensory deafness and congenital heart disease. Case : Reported a 3-year-old 6-month-old boy diagnosed with very severe degree sensorineural deafness and congenital heart disease based on anamnesis, physical examination and examination of OAE, BERA and ASSR for examination of auditory function) and echocardiography examination for examination of cardiac function. Conclusion : From the history, physical examination and examination of OAE, BERA, ASSR showed patients with very severe sensorineural hearing loss of the left and right ear and congenital heart disease, planned use of hearing aids or cochlear implantation and cardiac consul for CHD treatment.

Heterozygous variants in transmembrane channel-like 1 gene cause autosomal recessive nonsyndromic hearing loss.

Autosomal recessive non-syndromic hearing loss (ARNSHL) can cause severe or very severe pre-speech hearing loss. Transmembrane channel-like 1 (TMC1) gene is the sixth deafness gene discovered, but the precise extent of its protein structure and function is unknown. First, history collection, audiology examination and imaging examination were performed on the proband and his family members. Peripheral blood of proband and family members was collected, genomic DNA was extracted, exon high-throughput sequencing technology was used to detect the deafness gene mutation of the proband, and Sanger sequencing was performed to verify the TMC1 gene of the proband's parents. The proband was born with hearing impairment, normal tympanic function, inability to induce acoustic reflex in both ears (acoustic reflex threshold is 100 dBHL), and severe sensorineural deafness. One of his sisters has severe sensorineural hearing loss, and neither his parents nor his other sister is hearing impaired. High-throughput sequencing of the proband identified mutations at c.741+3_741+6delAAGT (splicing) and c.884C>T (p.A295V) of the TMC1 gene, two of which were heterozygous mutations. Sanger sequencing confirmed that the c.884C > T mutation was inherited from the mother, while the c.741+3_741+6delAAGT mutation was derived from the father. Prediction of amino acid function suggested that both mutations were pathogenic mutations. In conclusion, we found a new pathogenic complex heterozygous mutation of the TMC1 gene, which enriched the mutation spectrum of the TMC1 gene and provided a basis for genetic counseling and prenatal diagnosis of ARNSHL.

Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes

Objective: To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness. Methods: Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method. Results: The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband's mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion: This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.

Gray matter density changes in children with congenital severe sensorineural deafness: a voxel-based morphometric study.

Early hearing loss could cause abnormal brain development, which has been linked to the complex process known as cross-modal neuroplasticity. However, previous studies investigating the brain structure of infants with congenital severe sensorineural hearing loss (CSSHL) are scarce and have yielded inconsistent results. This study aimed to further explore the gray matter (GM) density changes in children with CSSHL. Fifteen children aged 0-5 years with CSSHL and 11 healthy children as controls (aged 0-5 years) were recruited. Each participant underwent a structural MRI scan. The voxel-based morphometry method was performed to evaluate GM density for each participant and analyze their characteristics. It was discovered that: (1) GM density of the right superior temporal gyrus and caudate in the CSSHL group was smaller than that of healthy controls (HC). However, GM density was larger in the left posterior central gyrus, superior frontal gyrus, inferior parietal lobule and right cerebellum in the CSSHL group compared with HC. (2) The GM density value of the left superior frontal gyrus and inferior parietal lobule was negatively correlated with age. However, the GM density value of the right superior temporal gyrus in the CSSHL group was positively correlated with age. Compared with HC, the GM density of CSSHL children was larger in somatosensory areas (including left superior frontal gyrus, posterior central gyrus, inferior parietal lobule and right cerebellum), whereas GM density was smaller in auditory-related areas (such as the right superior temporal gyrus and caudate). Moreover, GM density change was influenced by the duration of hearing deprivation.

Peculiarities of the acoustic reflex registration thresholds in relation to the parameters of the thresholds tone audiometry in patients with acute combat trauma

Aim: study of threshold ratios between indicators of acoustic impedance and threshold tonal audiometry in military personnel – participants in hostilities. Materials and methods: the results of audiometric and impedancemetric examinations of 43 servicemen aged 18 to 42 years who received combat acute trauma in the period March-August 2022 and 20 patients with severe sensorineural deafness (2, 3, 4 stages according international classification) of non-acutraumatic genesis as a comparison group. Results and their discussion: During the examination of 43 soldiers, it was found that with significant sensorineural hearing loss on both sides (3 and 4 stages according international classification), the patients registered a full-fledged acoustic reflex during ipsilateral and contralateral stimulation. When conducting an impedanceometric examination of patients in the comparison group, it was found that in most patients the acoustic reflex was not registered at all. Conclusions: 1. In combat acute acoustic trauma, it is possible to register acoustic middle-ear-muscle reflex with severe hearing loss, which may be caused by damage to the receptor part of the auditory analyzer and the accompanying symptom of the phenomenon of accelerated loudness, by a central mechanism, or by a combination of central and peripheral mechanisms. 2. Dissociation of acoustic middle-ear-muscle reflex threshold values and threshold tonal audiometry is a characteristic feature of acutraumatic damage to the auditory analyzer. 3. Identified features, such as registration of acoustic middle-ear-muscle reflex in severe hearing loss, dissociation of acoustic reflex thresholds and tonal audiometry may be useful for further study of the pathogenesis of combat acute trauma, which, in turn, will contribute to improving the quality of diagnosis and finding ways to correct disorders of the auditory system in individuals, who suffered as a result of hostilities.

Clinical features and genetic analysis of Dandy-Walker syndrome

BackgroundDandy-Walker syndrome (DWS) is a rare congenital malformation of the central nervous system (CNS), characterized by underdevelopment or dysplasia of the cerebellar vermis, expansion of the fourth ventricle and posterior fossa cistern. The incidence is aboutapproximately 1/25000–1/35000. At present, the etiology and pathogenesis of DWS are not completely clear. It is mostly considered to be a multifactorial genetic disease that is related to both genetic factors and environmental factors. There is no large sample size analysis of the chromosomal profile of DWS up to now. This study aims to provide clinical reference for prenatal diagnosis via summarizing the clinical features and pregnancy outcomes of Dandy-Walker syndrome.MethodsA total of 76 cases of foetal Dandy-Walker syndrome out of 19,506 pregnant women underwent cordocentesis or amniocentesis for genetic detection. Rapid prenatal karyotyping, single nucleotide polymorphism array (SNP-array) and BACs-on-Beads™ (BoBs) were performed for prenatal genetic diagnosis. The results of ultrasonography, genetic analysis and pregnancy outcome were recorded.ResultsOf the 76 cases, 19 were isolated DWS, while 57 cases were accompanied by other ultrasound-visible abnormalities. Ultrasound abnormalities of the CNS were most frequently observed, accompanied by DWS. Twenty-five out of 76 cases had chromosomal abnormalities, and the rate of chromosomal abnormalities increased in pregnant women of advanced maternal age or in combination with other ultrasound abnormalities. Of the 19 cases in the isolated DWS group, nine pregnant women chose to terminate the pregnancy, while seven cases continued the pregnancy and all infants were normal. Among the 57 pregnant women with pathological ultrasound manifestations other than foetal DWS, 44 chose to terminate the pregnancy, while 12 cases continued the pregnancy. Further follow-up revealed one newborn with postnatal neurodevelopmental delay. A female term neonate presented with very severe sensorineural deafness, and an infant died 7 days after birth with abnormal development of multiple organs.ConclusionsPregnant women with DWS in foetal ultrasonic examination should be offered a careful and comprehensive foetal ultrasound scan and further prenatal genetic testing including karyotype analysis and SNP-array. The prognosis of the foetus without chromosomal aberration is good in isolated DWS pregnancies but poor in nonisolated DWS pregnancies.

A Rare Case: Adenocarcinoma Bronchogenic Dextra Std IVB on Gefitinib (15 months) accompanied by Decreased Visual Acuity, Bilateral Sensorineural Deafness and Psychiatric Disorders with No Radiological Evidence of Brain Metastasis

Background: Leptomeningeal disease occurs in 3-5% of patients with lung cancer, mainly adenocarcinoma subtype. Adenocarcinoma is the most common histological finding in Asian women.
 Case: A 51-year-old woman with right-sided bronchogenic adenocarcinoma T4N3M1c Std IVB mutation(+) developed decreased vision, severe bilateral sensorineural deafness and psychiatric disorders after receiving Gefitinib 15 months. There was no evidence of brain metastasis from brain MRI. From evaluation of chest CT-scan, we found the disease was progressive and no Mutation Detected from ctDNA, so Gefitinib was discontinued.
 Conclusion: We found some difficulties in evaluating side effects of therapy and disease progression due to patient's condition in the form of decreased total vision, severe sensorineural deafness, and psychiatric disorders. However, because no radiological evidence of brain metastases was found, we suspect this patient suffered from leptomeningeal disease.
 Keywords: Lung Cancer, Adenocarcinoma, Gefitinib, Leptomeningeal Disease

Analysis of GJB2 Gene Mutations in 1330 Deafness Cases of Major Ethnic Groups in Northwest China.

Background: The GJB2 gene is the most common deafness gene, and epidemic characteristics have obvious racial specificity. Our study aimed to investigate the prevalence and ethnic specificity of the GJB2 gene in deafness in major ethnic groups in Northwest China, evaluate the value of molecular screening for deafness in minority populations, and explore the strategies and methods for genetic diagnosis. Methods: Ethics approval was obtained to collect 1330 cases of moderate to very severe nonsyndromic sensorineural deafness in northwestern China. The mutation characteristics of ethnic minorities were analyzed and compared with those of 464 patients with nonsyndromic sensorineural deafness among ethnic Han in the northwestern from research group by Sequence Scanner V25.0. Then, we analyzed the ethnic specificity of the mutations. Results: A total of 15 GJB2 sequence changes were detected in 1330 minority patients. The study showed that the allele frequency in Tibetan patients was significantly lower than that in Hui and Dongxiang patients, that in Uygur patients was significantly lower than that in Han and Hui patients, and that in Kazak and Tibetan patients was significantly lower than that in Han patients, and the differences between other ethnic groups were not statistically significant. Each ethnic group has a unique GJB2 gene mutation spectrum, and its hotspot mutation distribution has its own characteristics, with c.235delC, c.109 G > A, c.299-300delAT, and c.35delG being common. Conclusions: It has been confirmed that GJB2 gene mutation has a high prevalence in patients with nonsyndromic sensorineural hearing loss in Northwest China. Each ethnic group has a unique mutation spectrum for the GJB2 gene, which is related to its genetic background. It is necessary to develop a corresponding gene diagnosis strategy according to the hotspot mutations and mutation spectrum of each ethnic group.

The value of quantitative measurement of key structures of inner ear by HRCT in hearing evaluation of patients with congenital severe sensorineural deafness

Objective:Study on the value of quantitative measurement of key structures of inner ear by high resolution computer tomography（HRCT） in hearing evaluation of patients with congenital severe sensorineural hearing loss（SNHL）. Methods:A total of 90 children with extremely severe SNHL diagnosed and treated in Beilun District People's Hospital from January 2018 to February 2021 were collected as the experimental group. In the same period, 90 children（180 ears） with normal inner ear structure and hearing were scanned because of head trauma and suspected temporal bone fracture. Logistic univariate and multivariate regression analysis were used to analyze the factors affecting the occurrence of extremely severe SNHL. Based on the results of multivariate analysis, a Nomogram prediction model was established. The model before and after internal correction was evaluated by the receiver working characteristic curve. Results:Inner ear malformation, SSCC bone island width, LSCC bone island width and cochlear height were independent risk factors for extremely severe SNHL. The results of Nomogram predictive model showed that cochlear height 34 points, LSCC bone island width 19 points, SSCC bone island width 22 points, inner ear malformation 37 points, the total score（112 points） corresponding to the incidence of extremely severe SNHL（0.3%）. The actual C-index value of Nomogram prediction model is 0.858, the C-index of internal verification is 0.851, and the C-index of external verification is 0.847. The coincidence of the model is good. It is suggested that the model can effectively predict the risk factors of congenital extremely severe SNHL and has high prediction accuracy. Conclusion:The standardized measurement of SSCC bone island width, LSCC bone island width and cochlear height by HRCT is of great value in the diagnosis of microinner ear malformation in children with extremely severe SNHL.

Application Effect of Unilateral Cochlear Implantation Combined with Contralateral Hearing Aids on the Hearing and Speech Rehabilitation in Prelingual Deafness Children

Objective. The purpose of the study was to investigate the application effect of unilateral cochlear implantation combined with contralateral hearing aids on the hearing and speech rehabilitation in prelingual deafness children. Methods. In this study, a total of 78 children with severe or extremely severe sensorineural prelingual deafness admitted to our hospital from January 2015 to December 2017 were selected and divided into control group (n=39) and experimental group (n=39), according to the random number table. Among them, the children patients in the control group received dominant training after unilateral cochlear implantation, while the children patients in the experimental group received cochlear implantation combined with contralateral hearing aids; after that, the hearing and speech rehabilitation outcomes of the prelingual deafness children in both groups were compared and analyzed. Results. There were no statistically significant differences in the auditory thresholds of the children patients undergoing cochlear implantation between the two groups, while the auditory thresholds of contralateral ears of the children patients in the experimental group were significantly lower than those in the control group. The recognition rates of the initials, finals, tones and disyllables of the children patients in the experimental group were significantly higher than those in the control group, and the CPA and SIR scores of the children patients in the experimental group were significantly higher than those in the control group, with statistical significance (P < 0.05). Conclusions. Unilateral cochlear implantation combined with contralateral hearing aids can promote the hearing and speech rehabilitation in prelingual deafness children, with better clinical effect than the single unilateral cochlear implantation, and cochlear implantation have no interference in the work of contralateral hearing aids; therefore, this joint treatment method is worthy of wide application and promotion.

Long-term outcome of oral-aural rehabilitation in patients with cochlear implants

Background. Cochlear implantation is currently the most effective method for oral-aural rehabilitation in children with severe sensorineural hearing loss and deafness. Nevertheless, some controversies remain on timing of surgery and use of mono- and bilateral implants. Objectives . Assessment of the long-term results of oral-aural rehabilitation in children with mono- and bilateral cochlear implants depending on timing of the surgical intervention. Methods. The following oral-aural rehabilitation phases were scored in children with mono-and bilateral cochlear implants: “Language stage of speech perception and production” and “Understanding of coherent speech and complex text”. A retrospective assay used data on 98 patients following long-term oral-aural rehabilitation after cochlear surgery. Command ofmain language components and oral speech was assessed in detail against 12 skill learning criteria by psychoneurologists and teachers of the deaf. Statistical analyses were carried out with MS Office Excel 2010. Results . The “Language stage of speech perception and production” phase long-term scoring in children with bilateral cochlear implants demonstrated the skills of developing auditory memory, active (expressive) vocabulary, dialogic speech and voice control to account for an over 50% improvement in the cohort having had surgery under 3 years of age. In patients with monolateral implants, the additional distinctive skills were aural-visual and aural speech perception and command of coherent speech (over 60% difference vs. the cohort with surgery under 7 years of age). The “Understanding of coherent speech and complex text” phase scoring against three criteria was used to conclude on rehabilitation efficacy after cochlear implantation, approve early surgery and provide further counsel for social adaptation in cochlear implant patients. Conclusion . A comprehensive post-cochlear implant rehabilitation scoring against a number of key criteria provides a more consistent view of oral-aural skill learning. A detailed evaluation of the basic communication tools like command of the main language components and oral speech affirmed the feasibility of bilateral cochlear implantation in children under 3 years of age. The results were used to advance social adaptation in cochlear implant patients.

A follow-up study of abnormal mutation in neonatal deafness gene screening

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years' audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years' hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years' hearing follow-up. Conclusions: The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.

Analyses of audiological examination in children without auditory brainstem response

Objective: To investigate residual hearing of children severe and profound sensorineural deafness in whom wave V was not found in auditory brainstem response(ABR) testing, and to emphasize the importance of objective audiological tests. Methods: Two hundred and fifty-two children who were admitted to the Second Affiliated Hospital of Zhengzhou University between January 2015 and April 2018, with an average age of 20 months from 72 days to 4 years, received a full battery of objective audiological tests consisting of distortion product otoacoustic emission(DPOAEs), tympanometry, auditory brainstem responses(ABRs), 40 Hz auditory event related potential(40 HzAERP) and auditory steady-state response(ASSRs).There were 159 males(318 ears) and 93 females(186 ears). Residual hearing obtained by 40 HzAERP、ASSR of 252 children with sensorineural deafness was studied in relation to the absence of wave V in click ABR. SPSS 16.0 software was used to analyze the data. Results: Four hundred and forty-four ears of 504 ears have residual hearing of different degrees at different frequencies(88.1%),60 ears (11.9%) were found in whom responses was not found in 40 HzAERP、ASSR testing; Seventy-two ears(14.3%) in 38 patients were tested cochlear microphonic potentials (CMs). Conclusion: In children hearing evaluations,a full battery of objective audiological tests could better investigate residual hearing; The CMs were tested could provide the Audiotery Neuropathy diagnosis in infants with OAEs and ABR absent.

Advances in cochlear implantation for hereditary deafness caused by common mutations in deafness genes

Abstract The pathogenic factors of deafness are complex; more than 50% of cases are caused by genetic factors. Between 75% and 80% of cases of hereditary hearing impairment are autosomal recessive, 15% to 25% are autosomal dominant, and 1% to 2% are mitochondrial or X-linked. Cochlea implantation is the main method for treating severe and extremely severe bilateral sensorineural deafness and it is widely used in clinical treatment. As clinical cases of cochlea implantation accumulate, differences in the efficacy of implantation in individuals are emerging and attracting attention. In addition to residual hearing level, implantation age, and other factors, gene mutation is an important factor influencing postoperative rehabilitation in patients. With continuous progress in genetic testing technology for deafness, genetic diagnosis has become an important tool in preoperative evaluation and postoperative effect prediction in patients undergoing cochlear implantation. This article reviews the current status and future development of cochlear implantation in the treatment of hereditary deafness resulting from mutations in common deafness-causing genes.

A novel pathogenic variant in OSBPL2 linked to hereditary late-onset deafness in a Mongolian family

BackgroundTo investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease.MethodsFamily data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing.ResultsThe family is composed of a total of 6 generations, with 53 traceable individuals. In this family,19 of them were diagnosed with post lingual deafness with the age of onset between 10 and 40 years, displaying delayed and progressive hearing loss. Patients with hearing loss showed bilateral symmetry and mild to severe sensorineural deafness. The pattern of deafness inheritance in this family is autosomal dominant. Whole genome sequencing identified a novel pathogenic frameshift mutation, c.158_159delAA (p.Gln53Arg fs*100) in the gene OSBPL2 (Oxysterol-binding protein-related protein 2, NM_144498.2), which is absent from genomic data of 201 unrelated normal subjects. This pathogenic variant was further validated by Sanger sequencing, and was found to co-segregate in this family.ConclusionsWhole genome sequencing identified a two-nucleotide deletion in OSBPL2 (c.158_159delAA) as the pathogenic variant for deafness in the family. Our finding expands the mutational spectrum of OSBPL2 and contributes to the pathogenic variant list in genetic counseling for deafness screening.

Efficiency of the cochlear implantation in children with severe sensorineural hearing loss and deafness according to the data of speech audiometry in the free sound field and in the noise background

Relevance: Any kind of the hearing loss, especially in the childhood, affects the mental and intellectual development negatively as well as behavior and social position of a deaf patient in the hearing world. Cochlear implantation is the most effective and reliable method of medical and educational auditory-speech rehabilitation for both adults and children with severe hearing loss and deafness. One of the key performance indicators of the cochlear implantation is a result of speech audiometry, especially on the noise background. The aim is to study the state of auditory function according to the subjective audiometry in the noise background and the influence of various factors on the effectiveness of rehabilitation of the children after cochlear implantation. Materials and methods: The study involved 150 children with severe sensorineural hearing loss and deafness after cochlear implantation. In age, they ranged from 3 to 18 years old. Evaluation of the efficiency of cochlear implantation was carried out in several stages. All studies were done in the free-field with the cochlear implant on. At first, we performed the pure tone audiometry. Then we defined the 50% intelligibility threshold of numeral test. After that, we defined a word recognition percentage. And finally we defined the impact of masker on speech intelligibility at SPL of useful signal 50, 60 and 80 dB. Results: Based on the analysis of the received data, all children with severe sensorineural hearing loss and deafness after cochlear implantation were divided into 3 groups depending on the speech intelligibility. The first group (high efficiency of cochlear implantation) included 68 children (45,3%). This group was divided into two subgroups depending on the difference between the values of the speech intelligibility in the free sound field and in the noise background. The second group (average efficiency) consisted of 45 children (30%). The third group (low efficiency) were 37 children (24,7%). The influence of various factors on the efficiency of cochlear implantation was analyzed. Conclusion: Speech intelligibility in the noise background must be examinated in all children after cochlear implantation. The main factors affecting the effectiveness of cochlear implantation according to test of speech intelligibility in the noise background are the ethiology of hearing loss and duration of post-operation period. Results of speech intelligibility in the noise background test will help specialists who practice the rehabilitation of children after cochlear implantation (teachers for deaf, speech therapists) to pay attention to the decrease of speech intelligibility in children in the real conditions of communication and to focus their efforts on its improving with the appropriate methods.

Magnetic stem cell targeting to the inner ear

Severe sensorineural deafness is often accompanied by a loss of auditory neurons in addition to injury of the cochlear epithelium and hair cell loss. Cochlear implant function however depends on a healthy complement of neurons and their preservation is vital in achieving optimal results. We have developed a technique to target mesenchymal stem cells (MSCs) to a deafened rat cochlea. We then assessed the neuroprotective effect of systematically delivered MSCs on the survival and function of spiral ganglion neurons (SGNs). MSCs were labeled with superparamagnetic nanoparticles, injected via the systemic circulation, and targeted using a magnetized cochlea implant and external magnet. Neurotrophic factor concentrations, survival of SGNs, and auditory function were assessed at 1week and 4weeks after treatments and compared against multiple control groups. Significant numbers of magnetically targeted MSCs (>30MSCs/section) were present in the cochlea with accompanied elevation of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor levels (p<0.001). In addition we saw improved survival of SGNs (approximately 80% survival at 4weeks). Hearing threshold levels in magnetically targeted rats were found to be significantly better than those of control rats (p<0.05). These results indicate that magnetic targeting of MSCs to the cochlea can be accomplished with a magnetized cochlear permalloy implant and an external magnet. The targeted stem cells release neurotrophic factors which results in improved SGN survival and hearing recovery. Combining magnetic cell-based therapy and cochlear implantation may improve cochlear implant function in treating deafness.

Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome

AbstractReticular dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis, and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics, and outcome of HSCT were collected from centers in Europe, Asia, and North America for a total of 32 patients born between 1982 and 2011. Age at presentation was <4 weeks in 30 of 32 patients (94%). Grafts originated from mismatched family donors in 17 patients (55%), from matched family donors in 6 patients (19%), and from unrelated marrow or umbilical cord blood donors in 8 patients (26%). Thirteen patients received secondary or tertiary transplants. After transplantation, 21 of 31 patients were reported alive at a mean follow-up of 7.9 years (range: 0.6-23.6 years). All patients who died beyond 6 months after HSCT had persistent or recurrent agranulocytosis due to failure of donor myeloid engraftment. In the absence of conditioning, HSCT was ineffective to overcome agranulocytosis, and inclusion of myeloablative components in the conditioning regimens was required to achieve stable lymphomyeloid engraftment. In comparison with other SCID entities, considerable differences were noted regarding age at presentation, onset, and type of infectious complications, as well as the requirement of conditioning prior to HSCT. Although long-term survival is possible in the presence of mixed chimerism, high-level donor myeloid engraftment should be targeted to avoid posttransplant neutropenia.