Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct（EVA） using the linear mixed effect model（LMM）, providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type（Type C） demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans ; Vestibular Aqueduct/abnormalities* ; Genotype ; Sulfate Transporters ; Mutation ; Auditory Threshold ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Child, Preschool ; Hearing Loss/genetics* ; Hearing Tests ; Linear Models ; Infant

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with congenital deafness pedigree in conjunct with enlarged vestibular aqueduct. METHODS: Whole-exome sequencing was carried out for the proband to analyze the genes associated with hereditary deafness. Candidate variant was verified by Sanger sequencing of the proband's parents and her younger brother. RESULTS: The proband was found to harbor compound heterozygous variants including c.748dupG (p.Asp250Glyfs*30Asn) (pathogenic, PVS1+PM2+PP4) and c.879C>A (p.Ser293Arg) (likely pathogenic, PM2+PM3+PP1+PP4) of the FOXI1 gene, which has been associated with enlarged vestibular aqueduct (OMIM 600791). Both variants were unreported previously. The variants were respectively inherited from proband's parents whom had normal hearing. Her younger brother was heterozygous for the c.748dupG variant but also had normal hearing. CONCLUSION The compound heterozygous variants of the FOXI1 gene probably underlay the pathogenicity of congenital deafness and enlarged vestibular aqueduct in the proband. The co-segregation of the two variants with the hearing loss has facilitated genetic counseling and prenatal diagnosis for this pedigree.
China ; Deafness/genetics* ; Female ; Forkhead Transcription Factors/genetics* ; Hearing Loss, Sensorineural ; Humans ; Male ; Mutation ; Pedigree ; Pregnancy ; Vestibular Aqueduct/abnormalities*

OBJECTIVETo analyze mutations of SLC26A4 gene and explore their origins for a patient with enlarge vestibuar aqueduct syndrome.

METHODSClinical data and peripheral venous blood samples were collected from the patient and her parents. Genome DNA was extracted from the peripheral blood. All of the 21 exons of the SLC26A4 gene were amplified with PCR and subjected to directly sequencing.

RESULTSThe patient was found to have carried two mutant alleles of the SLC26A4 gene, namely c.1522A to G and c.1229C to T, which were inherited from her father and mother, respectively.

CONCLUSIONSLC26A4 c.1522A to G is likely to be a pathogenic mutation. Above results may facilitate genetic counseling and prenatal diagnosis for this family.

Adult ; Amino Acid Sequence ; Child ; Exons ; Female ; Hearing Loss, Sensorineural ; genetics ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Molecular Sequence Data ; Pedigree ; Vestibular Aqueduct ; abnormalities

OBJECTIVETo carry out mutation analysis and prenatal diagnosis for 12 families affected with hearing loss and enlarged vestibular aqueduct from southern Zhejiang province.

METHODSClinical data and peripheral venous blood samples of 38 members from the 12 families were obtained. Mutations of 4 genes, namely SLC26A4, GJB2, c.538C to T and c.547G to A of GJB3, m.1555A to G and m.1494C to T of 12S rRNA, were detected by PCR and Sanger sequencing. Maternal contamination was excluded by application of STR detection during prenatal diagnosis.

RESULTSAmong the probands from the 12 families, 11 were found to be compound heterozygotes or homozygotes and 25 were heterozygotes. All of the families were detected with IVS7-2A to G mutations, and 4 had a second heterozygous mutation (c.2168A to G of the SLC26A4 gene). Four rare pathogenic mutations, namely IVS5-1G to A, c.946G to T, c.1607A to G and c.2167C to G, were detected in another four families. In addition, the partner of proband from pedigree 3 was identified with compound heterozygous mutations of c.235delC and c.299-300delAT, and proband of pedigree 5 has carried a mutation of c.109G to A in GJB2. For SLC26A4 gene, prenatal diagnostic testing has revealed heterozygous mutations in 6 fetuses and compound heterozygous mutations in 2 fetuses.

CONCLUSIONIVS7-2A to G and c.2168A to G of the SLC26A4 gene were the most common mutations in southern Zhejiang. Such mutations can be found in most families affected with hearing loss and enlarged vestibular aqueduct, which may facilitate genetic counseling and prenatal diagnosis for such families.

Adolescent ; Adult ; Base Sequence ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Hearing Loss ; diagnosis ; embryology ; genetics ; Hearing Loss, Sensorineural ; diagnosis ; embryology ; genetics ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Vestibular Aqueduct ; abnormalities ; embryology ; Young Adult

OBJECTIVE: Analyze the data of the patients with sensorineural hearing loss in China and study the classification and incidence of inner ear malformationsby the high-resolution computed tomography. METHOD: The investigation took a retrospective review of CT findings relating to the 2,747 cases of outpatients. The inner ear malformations diagnosed by CT were classified according to the methods proposed by Sennaroglu. RESULT: (1)843 cases of inner ear malformations were found in 2747 cases of patients with sensorineural hearing loss by CT examination. The incidence of inner ear malformation was 30.69%(843/2747). (2) The epidemiological information of 843 cases of inner ear malformation according to Sennaroglu's classification was as follows: cochlea was 52. 31%(441/843), simple vestibular aqueduct was 40.33%(340/843), simple vestibular/ semicircular canal/internal auditory canal were 7. 35%(62/843) of the group. (3) 441 cases of cochlea malformation were consisted of these types of malformation: Michel deformity was 1.13% (5/441), cochlear aplasia was 1. 81% (8/441), common cavity deformity was 3. 17% (14/441), incomplete partition type I was 8. 62% (38/441), cochlea hypoplasia was 9. 07% (40/441) and incomplete partition type II was 76. 19% (336/441) of the group. CONCLUSION The results suggested that 30. 69% cases of inner ear malformation can be found in patients with sensorineural hearing loss, which is more higher than reported by the high-resolution computed tomography. Sennaroglu's classification is instructively significant in investigating the status of inner ear malformations.
China ; Cochlea ; Ear, Inner ; abnormalities ; Hearing Loss, Sensorineural ; etiology ; Humans ; Outpatients ; Retrospective Studies ; Semicircular Canals ; Temporal Bone ; Tomography, X-Ray Computed ; Vestibular Aqueduct ; Vestibule, Labyrinth

OBJECTIVE: To investigate imaging and audiology features of temporal bone and analyze the classification and prevalence of inner ear abnormalities in children with sensorineural hearing loss. METHOD: Children who were diagnosed with sensorineural hearing loss were examined by high resolution CT and the inner ear fluid of MRI. And each chart was retrospectively reviewed to determine the imaging and audiology features. RESULT: There were 125 patients(232 ears) found with inner ear malformation in 590 children with SNHL. About 21.71% of the inner ear malformation occurred in severe and profound hearing loss ears, and 12.85% occurred in r moderate hearing loss ears. The inner ear malformation rate in normal hearing ears were 13.59%. CONCLUSION CT and MRI examinations of temporal bone are important diagnostic tools to indentify inner ear malformations. Inner ear malformations are almost bilateral and hearing loss are profoud. Cochleo-vestibular malformations and large vestibular aqueduct are the 2 most frequent deformities. Among the children with SNHL, deformity rate in the severe and profound hearing loss ears is higher than that in moderate hearing loss ear. Inner ear malformations can exist in people with normal hearing.
Audiology ; Child ; Ear, Inner ; abnormalities ; Hearing Loss, Sensorineural ; congenital ; pathology ; Humans ; Magnetic Resonance Imaging ; Prevalence ; Retrospective Studies ; Temporal Bone ; Tomography, X-Ray Computed ; Vestibular Aqueduct ; abnormalities

OBJECTIVE: To investigate diagnostic value and clinical application of MRI in the children with sensorineural hearing loss (SNHL) before cochlear implantation. METHOD: MRI images of 80 children with the diagnosis of SHNL were retrospectively analyzed in combination with the latest classification of inner ear malformation. RESULT: There were 152 ears of inner ear malformation of 80 cases (160 ears), including 38 ears of cochlear malformation, 33 ears of vestibular malformation, 41 ears of semicircular canal malformation, 37 ears of vestibular aqueduct enlargement, 40 ears of internal auditory canal malformation, and 46 ears of cochlear nerve malformation. CONCLUSION MRI can provide detailed and reliable anatomical information for children with SNHL before cochlear implantation, and help to make the classification diagnosis. Therefore MRI is of great clinical significance for operation plan guidance and prognosis assessment.
Child ; Cochlear Implantation ; Cochlear Nerve ; pathology ; Hearing Loss, Sensorineural ; diagnosis ; pathology ; Humans ; Magnetic Resonance Imaging ; Retrospective Studies ; Semicircular Canals ; pathology ; Temporal Bone ; pathology ; Tomography, X-Ray Computed ; Vestibular Aqueduct ; abnormalities ; pathology

OBJECTIVE: To explore the found ways and first diagnosis age of children with large vestibular aqueduct, and their relations with hearing loss. METHOD: Medical histories of 122 cases of children diagnosed with large vestibular aqueduct by HRCT or MRI had been collected from January 2009 to April 2014 in our hospital children's hearing diagnosis center clinic. Found ways comprise of accepting universal newborn hearing screening (UNHS) group and unaccepting UNHS group. Accepting UNHS children were divided into two ears unpassing group, single ear unpassing group and passing group. The patients in unaccepting UNHS group were divided into not sensitive to sounds, speech stunting, sudden hearing loss, and other group. Analysis the relationship between the found ways and first diagnosis age and their relations with hearing loss. RESULT: There are 84 cases (68.85%) accepting UNHS, the average age of first diagnosis was (17.24 ± 17.08) months; 37 cases (31.15%) are not accepting UNHS. The average age of first diagnosis was (30.92 ± 18.21) months. The average first diagnosis age of accepting UNHS group was more earlier than the unaccepting UNHS group. The difference was statistically signif- icant (P < 0.01). There were 57 cases (67.85%) whose two ears not pass UNHS; 15 cases (17.86%) single ear not pass; namely the referral rate was 85.71%; 12 cases (14.29%) pass the test. The first diagnosis age of passing UNHS group was more later than two ears unpassing group (P < 0.001). In the unaccepting UNHS group, the average first diagnosis age of not sensitive to sounds group (19.69 ± 11.16 months) was more earlier than words dysplasia group (37.13 ± 15.62 months) and sudden hearing loss group (47.40 ± 24.70 months) (P < 0.01). The difference in the degree of hearing loss between accepting UNHS and unaccepting UNHS group had no statistical significance (P > 0.05). In unaccepting UNHS group ,the average first diagnosis age of the mild-to-moderate hearing loss group was later than the very severe hearing loss group (P < 0.01). CONCLUSION Most of large vestibular aqueduct children can be found and receive diagnosis early by UNHS. But part of these patients with late-onset or progressive hearing loss, especially these with mild-to-moderate hearing loss cannot be found early, which should arouse our attention.
Child, Preschool ; Deafness ; Early Diagnosis ; Hearing Loss ; etiology ; Hearing Loss, Sudden ; Hearing Tests ; Humans ; Infant ; Infant, Newborn ; Neonatal Screening ; Vestibular Aqueduct ; abnormalities

OBJECTIVE: Explore the relationship between the pathogenic mutations of SLC26A4 gene and inner ear malformation, and analyze the feasibility of genetic testing to help current diagnosis in part of children with sensorineural hearing loss. METHOD: 2094 cases of children were detected by SLC26A4 with the method of DNA sequence. CT phenotypes of those children were classified according to the method proposed by Sennaroglu. We analyzed the relationship between the pathogenic mutations of gene and the CT phenotypes. RESULT: (1) 685 cases of inner ear malformations were found in 2094 cases of children with sensorineural hearing loss by CT examination (371 cases of cochlea malformation were consisted of the follow types of malformation. Michel deformity was 6 cases, cochlea aplasia was 8 cases, common cavity deformity was 12 cases, incomplete partition type I was 27 cases, cochlea hypoplasia was 30 cases and Mondini malformation was 288 cases); Vestibular aqueduct was 265 cases; Vestibular/semicircular canal/internal auditory canal were 49 cases, normal was 1409 cases. (2) The DNA sequence results revealed that 465 cases carried pathogenic mutations (Bi-allelic mutations) of SLC26A4 gene, among which 135 cases were homozygous, 330 cases were compound heterozygous. (3) Pathogenic mutations of SLC26A4 gene detected 100% (465/465) in the group related to vestibular aqueduct malformation. CONCLUSION The results suggest that pathogenic mutation of SLC26A4 gene is closely related to the CT phenotype of vestibular aqueduct malformation. Detecting of pathogenic mutations for hearing loss is binging the possibility to identify children with inner malformations at an early stage. As a consequence, it will improve the current diagnosis and therapeutical option.
Alleles ; Child ; Cochlea ; Deafness ; Ear, Inner ; abnormalities ; Genetic Testing ; Hearing Loss ; Hearing Loss, Sensorineural ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; Phenotype ; Semicircular Canals ; Sulfate Transporters ; Temporal Bone ; Vestibular Aqueduct ; Vestibule, Labyrinth