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

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.
Humans ; Pedigree ; China ; Deafness/genetics* ; Hearing Loss/genetics* ; Phenotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Myosins/genetics*

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.
Humans ; Deafness/genetics* ; Hearing Loss, Sensorineural/diagnosis* ; Phenotype ; Metabolic Diseases/genetics* ; Genetic Counseling

Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.
Humans ; Audiometry, Pure-Tone ; Deafness/complications* ; Hearing Loss, Sensorineural/diagnosis* ; Hearing Loss, Sudden/diagnosis* ; Hyperlipidemias/complications* ; Lipids

Objective: To explore the change of hearing threshold of workers exposed to noise, establish an individual-based hearing loss early warning model, accurately and differentiated the health of workers exposed to noise. Methods: In September 2019, all physical examination data of 561 workers exposed to noise from an enterprise were collected since their employment. Three indicators of average hearing threshold of the better ear, namely, at high frequency, 4000 Hz and speech frequency, were constructed. The generalized estimating equation (GEE) was used to adjust gender and age and establish the warning model of each indicator. Finally, sensitive indicators and warning models were screened according to AUC and Yoden index. Results: Among the 561 workers exposed to noise, 26 (4.6%) workers had hearing loss. The sensitivity indicators were the average hearing threshold at speech frequency ≥20 dB, high frequency ≥30 dB and 4000 Hz ≥25 dB. The AUC of each index was 0.602, 0.794 and 0.804, and the Youden indexes were 0.204, 0.588 and 0.608, respectively. In GEE of hearing loss warning models, high-frequency hearing threshold ≥20 dB and 4000 Hz hearing threshold ≥25 dB were the optimal models, with AUC of 0.862. Conclusion: Combined with the changes of individual hearing threshold over the years, can accurately assess the risk of individual hearing loss of workers exposed to noise.
Humans ; Hearing Loss, Noise-Induced/diagnosis* ; Noise, Occupational/adverse effects* ; Audiometry ; Deafness ; Employment ; Occupational Exposure/adverse effects* ; Occupational Diseases/diagnosis*

Humans ; Hearing Loss/genetics* ; Deafness/genetics* ; Counseling ; China ; Genetic Counseling ; Mutation