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*

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.
Humans ; Child ; Connexins/genetics* ; Connexin 26/genetics* ; Hearing Loss, Sensorineural/diagnosis* ; Mutation ; Usher Syndromes ; Hearing Loss, Bilateral ; Audiometry, Pure-Tone ; Intercellular Signaling Peptides and Proteins

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

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.
Child ; Humans ; Mutation Rate ; Membrane Transport Proteins/genetics* ; China ; Hearing Loss, Sensorineural/diagnosis* ; Mutation ; Vestibular Aqueduct ; Vestibular Diseases/pathology* ; Deafness/genetics*

OBJECTIVE: To explore the clinical phenotype and genetic features of two children with MEGDEL syndrome due to variants of the SERAC1 gene. METHODS: Two children who had presented at the Fujian Medical University Union Hospital respectively on July 14, 2020 and July 28, 2018 were selected as the study subjects. Clinical features and results of genetic testing were retrospectively analyzed. RESULTS: Both children had featured developmental delay, dystonia and sensorineural deafness, along with increased urine 3-methylglutaric acid levels. Magnetic resonance imaging revealed changes similar to Leigh-like syndrome. Gene sequencing revealed that both children have harbored pathogenic compound heterozygous variants of the SERAC1 gene, including c.1159C>T and c.442C>T in child 1, and c.1168C>T and exons 4~9 deletion in child 2. CONCLUSION Children with MEGDEL syndrome due to SERAC1 gene variants have variable clinical genotypes. Delineation of its clinical characteristics and typical imaging changes can facilitate early diagnosis and treatment. Discovery of the novel variants has also enriched the spectrum of SERAC1 gene variants.
Humans ; Retrospective Studies ; Metabolism, Inborn Errors ; Hearing Loss, Sensorineural/genetics* ; Dystonia ; Carboxylic Ester Hydrolases