Cochlear nerve deficiency（CND） is a rare inner ear malformation characterized by a hypoplastic or absent cochlear nerve, resulting in variable hearing loss or total deafness, depending on the quantity of nerve fibers present. About 18% of congenital hearing loss are associated with CND. It is a disease of uncertain cause. The outcome of auditory implant in CND patients varies widely. This article will discuss the related issues of CND.
Humans ; Cochlear Nerve/abnormalities* ; Cochlear Implants ; Child ; Cochlear Implantation/methods* ; Deafness ; Hearing Loss

Objective:This study aimed to compare the effects of cochlear implantation（CI） on vestibular function in patients with large vestibular aqueduct syndrome（LVAS） and in patients with extremely severe deafness with normal inner ear structure. Methods:A total of 28 LVAS patients and 28 patients with normal inner ear structure who suffered from extremely severe deafness were selected. The parameters of caloric tests, bone conduction evoked cervical vestibular-evoked myogenic potentials（cVEMP）, bone conduction evoked ocular vestibular-evoked myogenic potentials（oVEMP） and video head impulse tests（v-HIT） were compared between the two groups before and after CI. The data were analyzed using SPSS 26.0 software. Results:There was no significant difference in the results of the preoperative caloric test, v-HIT, and oVEMP（P1, N1） between the LVAS group and the control group（P>0.05）. Compared to the control group, the LVAS group exhibited a shorter cVEMP P1[（13.41±0.71）ms vs （16.28±0.89）ms, P<0.000 1], shorter N1[（19.83±0.54）ms vs （28.18±1.56）ms, P<0.000 1], higher amplitude[（123.60±83.80）μV vs （73.92±79.85）μV, P=0.049 4] and higher oVEMP amplitude[（16.60±13.87）μV vs （9.96±10.47）μV, P=0.028 5] before CI. The abnormal rate of caloric test increased in both groups after CI（25.00% vs 57.14%, P=0.028 8, 32.14% vs 82.14%, P=0.000 3, respectively）. There was no significant difference in the v-HIT parameters in both groups before and after the operation. As for the LVAS group, there was no statistically significant difference in cVEMP and oVEMP induction rates before and after operation. In the control group, there was a decrease in cVEMP induction rate（96.42% vs 64.28%, P=0.005 2） and oVEMP induction rate（96.42% vs 57.14%, P=0.000 9） after CI. LVAS group showed a shorter cVEMP P1[（13.41±0.71）ms vs （10.30±0.60）ms, P<0.000 1]; shorter cVEMP N1[（19.86±0.53）ms vs （18.97±1.33）ms, P=0.004 7]; decreased amplitude[（124.50±84.86）μV vs （64.35±61.57）μV, P=0.001 0] and shorter oVEMP amplitude[（15.92±13.03）μV vs （9.16±9.20）μV, P=0.009 9] after CI. The oVEMP N1 in the control group was longer than that before operation[（11.73 ± 0.91）ms vs （13.35 ± 2.60）ms, P=0.019 6], whereas there was no significant difference in other VEMP parameters after CI. Conclusion:Before CI, there was no significant difference in the results of the caloric test and v-HIT between the LVAS group and the control group, but the LVAS group exhibited increased sensitivity to acoustic stimulation-induced myogenic potentials. After CI, the function of the semicircular canal was impaired in both groups in the low-frequency area, and remained largely unaffected in the high-frequency area. Additionally, the function of the otolith in the LVAS group was less affected than that in the control group after CI, which may be related to the fact that the enlarged vestibular aqueduct of the LVAS patients acted as the third window of the inner ear.
Humans ; Vestibular Aqueduct/physiopathology* ; Cochlear Implantation ; Male ; Female ; Vestibular Evoked Myogenic Potentials ; Deafness/physiopathology* ; Child ; Adolescent ; Adult ; Young Adult ; Hearing Loss, Sensorineural/physiopathology* ; Vestibular Function Tests

Objective:To study whether the auditory rehabilitation effect and quality of life of elderly patients have improved after cochlear implantation. Methods:Selected 36 elderly deafness patients over 60 years during the period January 2020 to December 2022, After exclusion of surgical contraindications, a minimally invasive cochlear implant was performed. Using the auditory behavior grading-Ⅱ（CAP-Ⅱ）, the Nijmegen cochlear implant scale（NCIQ）, the scores of preoperative, postoperative 6 months and postoperative 18 months of cochlear implantation in 36 elderly deafness patients were collected through questionnaire survey, and statistical analysis was conducted, compare the auditory ability and quality of life of elderly patients after cochlear implantation. Results:The preoperative score of CAP-Ⅱ （2.50±0.85） and the total score of NCIQ （23.73±2.12）; the CAP-Ⅱ score at the sixth postoperative month was （4.39±1.02） and the NCIQ total table score （40.55±3.52）. The CAP-Ⅱ score at the eighteen postoperative months was （5.97±1.28）, NCIQ total table （57.36±4.02）, and the highest score. Statistically significant difference per group（P<0.05）. Conclusion:After cochlear implantation in elderly patients with deafness, their auditory ability, basic sound perception, social ability, self-confidence and other quality of life were significantly improved.
Humans ; Cochlear Implantation ; Aged ; Quality of Life ; Cochlear Implants ; Middle Aged ; Deafness/surgery* ; Postoperative Period ; Surveys and Questionnaires ; Male ; Female ; Treatment Outcome

CREBBP gene encodes the transcriptional co-activator CREB-binding protein. This protein can participate in cell growth, differentiation and development through a variety of signal transduction pathways. Variants in this gene may cause syndromic deafness by affecting signal transduction pathways and development of skeletal and nervous systems. This review has summarized the structure and function of the CREBBP gene and the pathogenetic mechanism of syndromic deafness caused by CREBBP gene variants, with an aim to provide a basis for clinical diagnosis and treatment.
Humans ; CREB-Binding Protein/chemistry* ; Deafness/genetics* ; Mutation ; Animals ; Syndrome ; Signal Transduction

The SMPX (small muscle protein X-linked) gene encodes a small-molecular-weight protein that is mainly expressed in skeletal and cardiac muscles and is involved in cytoskeletal dynamics and mechanical stress responses. In recent years, missense variants of the SMPX gene have been identified as the cause of a novel X-linked distal myopathy (Distal myopathy 7). This article has systematically reviewed the molecular functions, variant types, and pathological mechanisms of the SMPX gene by integrating its clinical classification, molecular pathological evidence, and experimental model data, and revealed its pathgenetic mechanism through protein aggregation, dynamic dysregulation of stress granules, abnormal Rac1/p38 signaling pathways, and future research directions.
Humans ; Mutation ; Muscle Proteins/metabolism* ; Deafness/genetics* ; Animals ; Muscular Diseases/genetics* ; Genes, X-Linked

OBJECTIVE: To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms. METHODS: A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents. CONCLUSION The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.
Humans ; Pedigree ; Male ; Female ; Asian People/genetics* ; Cadherins/genetics* ; Exome Sequencing ; Deafness/genetics* ; Mutation ; China ; Adult ; Cadherin Related Proteins ; Hearing Loss, Sensorineural/genetics* ; East Asian People

Genetic counseling for hearing loss today originated from decoding the genetic code of hereditary hearing loss, which serves as an effective strategy for preventing hearing loss and constitutes a crucial component of the diagnostic and therapeutic framework. This paper described the main principles and contents of genetic counseling for hearing loss, the key points of counseling across various genetic models and its application in tertiary prevention strategies targeting hearing impairment. The prospects of an AI-assisted genetic counseling decision system and the envisions of genetic counseling in preventing hereditary hearing loss were introduced. Genetic counseling for hearing loss today embodies the hallmark of a new era, which is inseparable from the advancements in science and technology, and will undoubtedly contribute to precise gene intervention!
Humans ; Genetic Counseling ; Deafness/genetics* ; Hearing Loss/diagnosis* ; Hearing Loss, Sensorineural/genetics*

Humans ; Hearing Loss, Sensorineural/diagnosis* ; Deafness ; Mutation

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
Humans ; Connexins/genetics* ; Connexin 26/genetics* ; Hearing Loss, Central/genetics* ; Deafness/genetics* ; Mutation

Objective:To dentify the genetic and audiological characteristics of families affected by late-onset hearing loss due to GSDMEgene mutations, aiming to explore clinical characteristics and pathogenic mechanisms for providing genetic counseling and intervention guidance. Methods:Six families with late-onset hearing loss from the Chinese Deafness Genome Project were included. Audiological tests, including pure-tone audiometry, acoustic immittance, speech recognition scores, auditory brainstem response, and distortion product otoacoustic emission, were applied to evaluate the hearing levels of patients. Combining with medical history and physical examination to analyze the phenotypic differences between the probands and their family members. Next-generation sequencing was used to identify pathogenic genes in probands, and validations were performed on their relatives by Sanger sequencing. Pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics Guidelines. Meanwhile, the pathogenic mechanisms of GSDME-related hearing loss were explored combining with domestic and international research progress. Results:Among the six families with late-onset hearing loss, a total of 30 individuals performed hearing loss. The onset of hearing loss in these families ranged from 10 to 50 years（mean age: 27.88±9.74 years）. In the study, four splicing mutations of the GSDME were identified, including two novel variants: c. 991－7C>G and c. 1183+1G>T. Significantly, the c. 991－7C>G was a de novo variant. The others were previously reported variants: c. 991-1G>C and c. 991-15_991-13del, the latter was identified in three families. Genotype-phenotype correlation analysis revealed that probands with the c. 991－7C>G and c. 1183+1G>T performed a predominantly high-frequency hearing loss. The three families carrying the same mutation exhibited varying degrees of hearing loss, with an annual rate of hearing deterioration exceeding 0.94 dB HL/year. Furthermore, follow-up of interventions showed that four of six probands received intervention（66.67%）, but the results of intervention varied. Conclusion:The study analyzed six families with late-onset non-syndromic hearing loss linked to GSDME mutations, identifying four splicing variants. Notably, c. 991－7C>G is the first reported de novo variant of GSDME globally. Audiological analysis revealed that the age of onset generally exceeded 10 years,with variable effectiveness of interventions.
Humans ; Adolescent ; Young Adult ; Adult ; Child ; Hearing Loss, Sensorineural/diagnosis* ; Deafness/genetics* ; Mutation ; Hearing Loss/genetics* ; Pedigree