Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Family of H723R Mutation for SLC26A4 Associated with Enlarged Vestibular Aqueduct Syndrome.

ABSTRACT: Recessive mutations of the SLC26A4 (PDS) gene on chromosome 7q31 can cause sensorineural deafness with goiter (Pendred syndrome, OMIM 274600) or NSRD with goiter (at the DFNB4 locus, OMIM 600791). H723R (2168A>G) is the most commonly reported SLC26A4 mutations in Korean and Japanese and known as founder mutation. We recently experienced one patient with enlarged vestibular aqueduct syndrome. The genetic study showed H723R homozygous in the proband and H723R heterozygous mutation in his family members. The identification of a disease-causing mutation can be used to establish a genotypic diagnosis and provide important information to both families and their physicians.

SUBMITTER: Kim S

PROVIDER: S-EPMC2702731 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A Family of H723R Mutation for SLC26A4 Associated with Enlarged Vestibular Aqueduct Syndrome.

Kim Sunghee S Song Dae Gun DG Bae Jae Woong JW Choi Soo-Young SY Kim Un-Kyung UK Choi Young Jun YJ Lee Kyu Yup KY Lee Sang Heun SH Lee Jung Rae JR

Clinical and experimental otorhinolaryngology 20090629 2

Recessive mutations of the SLC26A4 (PDS) gene on chromosome 7q31 can cause sensorineural deafness with goiter (Pendred syndrome, OMIM 274600) or NSRD with goiter (at the DFNB4 locus, OMIM 600791). H723R (2168A>G) is the most commonly reported SLC26A4 mutations in Korean and Japanese and known as founder mutation. We recently experienced one patient with enlarged vestibular aqueduct syndrome. The genetic study showed H723R homozygous in the proband and H723R heterozygous mutation in his family me ...[more]

PMID: 19565036

Similar Datasets

Mutation analysis of SLC26A4 in mainland Chinese patients with enlarged vestibular aqueduct.

Project description:OBJECTIVE:We have characterized the spectrum of SLC26A4 mutations and clinical features in a population of mainland Chinese patients with nonsyndromic sensorineural hearing loss (SNHL) and enlarged vestibular aqueduct (EVA). STUDY DESIGN:Cross-sectional clinical genetic study. SETTING:Tertiary care outpatient otolaryngology clinic. METHODS:A total of 32 subjects identified with bilateral EVA using high-resolution CT were screened for mutations in SLC26A4 by denaturing high-performance liquid chromatography and direct sequencing methods. RESULTS:A total of 13 different mutations were identified in the SLC26A4 gene, five of which are novel. A total of 88 percent of the patients harbored biallelic mutations, 11 patients were homozygotes, and 17 were compound heterozygotes. Four patients were found to carry a single SLC26A4 mutation. The IVS7-2A>G mutation was the most frequent, accounting for 60 percent of the mutant alleles. We have not found any correlations between the type of SLC26A4 mutations and the type, degree, and progression of hearing loss. There are significant proportions of patients with asymmetric (26%), progressive (32%), or fluctuating hearing loss (21%). CONCLUSION:Our data confirm the high prevalence of SLC26A4 mutations in Chinese patients with SNHL and EVA. We could not establish any relationship between genotype and phenotype. However, the high incidence of asymmetric, progressive, and fluctuating hearing loss found in the current study indicates that patients with those features should be routinely screened for SLC26A4 mutation in addition to diagnosis of EVA using CT or MRI.

| S-EPMC3309400 | biostudies-literature

A Novel Frameshift Mutation of <i>SLC26A4</i> in a Korean Family With Nonsyndromic Hearing Loss and Enlarged Vestibular Aqueduct.

Project description:ObjectivesWe aimed to identify the causative mutation for siblings in a Korean family with nonsyndromic hearing loss (HL) and enlarged vestibular aqueduct (EVA). The siblings were a 19-year-old female with bilateral profound HL and an 11-year-old male with bilateral moderately severe HL.MethodsWe extracted genomic DNA from blood samples of the siblings with HL, their parents, and 100 controls. We performed mutation analysis for SLC26A4 using direct sequencing.ResultsThe two siblings were compound heterozygotes with the novel mutation p.I713LfsX8 and the previously described mutation p.H723R. Their parents had heterozygous mono-allelic mutations. Father had p.I713LfsX8 mutation as heterozygous, and mother had p.H723R mutation as heterozygous. However, novel mutation p.I713LfsX8 was not detected in 100 unrelated controls.ConclusionBoth mutations identified in this study were located in the sulfate transporter and anti-sigma factor antagonist domain, the core region for membrane targeting of SulP/SLC26 anion transporters, which strongly suggests that failure in membrane trafficking by SLC26A4 is a direct cause of HL in this family. Our study could therefore provide a foundation for further investigations elucidating the SLC26A4-related mechanisms of HL.

| S-EPMC5327591 | biostudies-literature

Hearing loss associated with enlarged vestibular aqueduct and zero or one mutant allele of SLC26A4.

Project description:OBJECTIVES/HYPOTHESIS:To characterize the severity and natural history of hearing loss, and the prevalence of having a cochlear implant in a maturing cohort of individuals with enlarged vestibular aqueduct (EVA) and zero or one mutant allele of SLC26A4. STUDY DESIGN:Prospective cohort study of subjects ascertained between 1998 and 2015 at the National Institutes of Health Clinical Center. METHODS:Study subjects were 127 individuals (median age, 8 years; range, 0-59 years) with EVA in at least one ear. RESULTS:Ears with EVA and zero or one mutant allele of SLC26A4 had mean 0.5/1/2/4-kHz pure-tone averages of 62.6 and 52.9 dB HL, respectively, in contrast to EVA ears with two mutant alleles of SLC26A4 (88.1 dB HL; P < .01). This association was independent of age, sex, or side of EVA (P < .001). Natural history of hearing loss was not associated with number of mutant alleles (P = .94). The prevalence of having a cochlear implant was nine (12%) of 76, two (13%) of 15, and 12 (38%) of 32 subjects with zero, one, and two mutant alleles, respectively (P = .00833). This association was not independent (P = .534) but reflected underlying correlations with age at time of first audiogram (P = .003) or severity of hearing loss (P = .000). CONCLUSIONS:Ears with EVA and zero or one mutant allele of SLC26A4 have less severe hearing loss, no difference in prevalence of fluctuation, and a lower prevalence of cochlear implantation in comparison to ears with two mutant alleles of SLC26A4. LEVEL OF EVIDENCE:NA Laryngoscope, 127:E238-E243, 2017.

| S-EPMC6224160 | biostudies-literature

Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome.

Project description:Mutations in SLC26A4 cause nonsyndromic hearing loss associated with an enlarged vestibular aqueduct (EVA, also known as DFNB4) and Pendred syndrome (PS), the most common type of autosomal-recessive syndromic deafness. In many patients with an EVA/PS phenotype, mutation screening of SLC26A4 fails to identify two disease-causing allele variants. That a sizable fraction of patients carry only one SLC26A4 mutation suggests that EVA/PS is a complex disease involving other genetic factors. Here, we show that mutations in the inwardly rectifying K(+) channel gene KCNJ10 are associated with nonsyndromic hearing loss in carriers of SLC26A4 mutations with an EVA/PS phenotype. In probands from two families, we identified double heterozygosity in affected individuals. These persons carried single mutations in both SLC26A4 and KCNJ10. The identified SLC26A4 mutations have been previously implicated in EVA/PS, and the KCNJ10 mutations reduce K(+) conductance activity, which is critical for generating and maintaining the endocochlear potential. In addition, we show that haploinsufficiency of Slc26a4 in the Slc26a4(+/-) mouse mutant results in reduced protein expression of Kcnj10 in the stria vascularis of the inner ear. Our results link KCNJ10 mutations with EVA/PS and provide further support for the model of EVA/PS as a multigenic complex disease.

| S-EPMC2681005 | biostudies-literature

Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct.

Project description:ObjectivesTo investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families.MethodsSanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted.ResultsThe results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function.ConclusionIn summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.

| S-EPMC6315218 | biostudies-literature

Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next-generation sequencing of the SLC26A4 gene.

Project description:BackgroundThe enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients.MethodsThus, in this study, we designed a new molecular diagnosis panel for EVA based on multiplex PCR enrichment and next-generation sequencing of the exon and flanking regions of SLC26A4. A total of 112 hearing loss families with EVA were enrolled and the pathogenicity of the rare variants detected was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines.ResultsOur results showed that 107/112 (95.54%) families carried SLC26A4 biallelic mutations, 4/112 (3.57%) carried monoallelic variants, and 1/112 (0.89%) had none variant, resulting in a diagnostic rate of 95.54%. A total of 49 different variants were detected in those patients and we classified 30 rare variants as pathogenic/likely pathogenic, of which 13 were not included in the Clinvar database.ConclusionOur diagnostic panel has an increased diagnostic yield with less cost, and the curated list of pathogenic variants in the SLC26A4 gene can be directly used to aid the genetic counseling to patients.

| S-EPMC8404235 | biostudies-literature

Functional Testing of SLC26A4 Variants-Clinical and Molecular Analysis of a Cohort with Enlarged Vestibular Aqueduct from Austria.

Project description:The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants. In this group, four uncharacterized sequence alterations within the SLC26A4 coding region were found. Three of these lead to protein variants with abnormal functional and molecular features, while one should be considered with no pathogenic potential. Pathogenic SLC26A4 sequence alterations were only found in 12% of patients. SLC26A4 sequence alterations commonly found in other Caucasian populations were not detected. This survey represents the first study on the prevalence and spectrum of SLC26A4 sequence alterations in an Austrian cohort and further suggests that genetic testing should always be integrated with functional characterization and determination of the molecular features of protein variants in order to unequivocally identify or exclude a causal link between genotype and phenotype.

| S-EPMC5796158 | biostudies-literature

A newly identified mutation (c.2029 C > T) in SLC26A4 gene is associated with enlarged vestibular aqueducts in a Chinese family.

Project description:BackgroundThe enlarged vestibular aqueduct (EVA), associated with mutations in the SLC26A4 gene, characterized by non-syndromic hearing loss, is an autosomal recessive disorder. Here, we intended to investigate genetic causes of hearing loss in a Han Chinese man.MethodFirst, whole-exome sequencing was performed to identify the gene mutations responsible for hearing loss in the proband. Sanger sequencing was used to verify the candidate mutations detected in the family. Next, we collected blood samples and clinical data from the three-generation pedigree. Finally, SLC26A4 mRNA and protein expression levels were detected by qPCR and western blotting.ResultThe proband suffered from bilateral progressive sensorineural hearing loss with EVA. The sequence analysis of SLC26A4 revealed that the proband and his sister both harbored a compound heterozygous mutation of c.2168A > G/c.2029C > T, inherited from their father and mother respectively. c.2029C > T mutation has not been recorded in the relevant literature previously. Relative mRNA levels of the SLC26A4 gene in individuals carrying a compound heterozygous mutation were significantly lower compared to a heterozygous mutation. SLC26A4 protein levels of 293t cells which transfected with recombinant plasmids [GV219-SLC26A4-mut (c.2029C > T) and GV219-SLC26A4-mut (c.2168A > G/c.2029C > T)] were significantly lower than normal control recombinant plasmids (GV219-SLC26A4-wt).ConclusionThis study found a novel heterozygous mutation c.2029 (exon17) C > T compound with c.2168 (exon19) A > G in the SLC26A4 gene in a patient with EVA. The c.2029 (exon17) C > T mutation is proved to be pathogenic. This finding broadens the spectrum of variants in SLC26A4 gene.

| S-EPMC8898487 | biostudies-literature

[Difference of <i>SLC26A4</i> gene mutation frequency between patients with large vestibular aqueduct syndrome and/or Mondini dysplasia].

Project description:Objective:The purpose of this study was to evaluate the mutation frequency of SLC26A4 gene in patients with enlarged vestibular aqueduct syndrome（EVAS） and/or Mondini dysplasia（MD）, so as to provide evidence for molecular diagnosis of deafness. Methods:In total, 74 patients with sensorineural hearing loss were included in this study. All patients underwent thin-layer CT examination of temporal bone. The coding exons of SLC26A4 were analyzed by second-generation sequencing in all subjects. Results:Among them, 37 patients with EVAS and MD（E+M group）, 28 patients with EVAS and without MD（E group）, and 9 patients with isolated MD（M group） were identified. In 74 cases, 66 cases（89.2%） were found to have mutation, including 64 cases（86.5%） of biallelic mutation and two cases（2.7%） of single allele mutation. The detection rate of SLC26A4 in different groups was statistically significant（P<0.001）. The mutation rate in group M was significantly lower than that in Group E and E+M（P<0.001）. In Group E, 27 cases（96.4%） had SLC26A4 biallelic mutations and one case（3.6%） had SLC26A4 single allele mutation, respectively; in Group E+M, 37 cases（100%） had SLC26A4 biallelic mutations; in group M, only one patient（11.1%） carried monoallelic mutations of the SLC26A4 gene. Conclusion:There are totally different pathogenesis in Chinese EVAS patients with or without MD, or isolated MD. Early clinical genetic diagnosis of patients with EVAS and/or MD helps to provide accurate information about the genetic causes of hearing loss, provide genetic counseling, and implement appropriate disease control and prevention measures. Next generation sequencing technology plays an increasingly important role in molecular diagnosis of deafness.

| S-EPMC10127702 | biostudies-literature

Slc26a4 expression prevents fluctuation of hearing in a mouse model of large vestibular aqueduct syndrome.

Project description:SLC26A4 mutations cause fluctuating and progressive hearing loss associated with enlargement of the vestibular aqueduct (EVA). SLC26A4 encodes a transmembrane anion exchanger called pendrin expressed in nonsensory epithelial cells of the lateral wall of cochlea, vestibular organs and endolymphatic sac. We previously described a transgenic mouse model of EVA with doxycycline (dox)-inducible expression of Slc26a4 in which administration of dox from conception to embryonic day 17.5 (DE17.5) resulted in hearing fluctuation between 1 and 3months of age. In the present study, we hypothesized that Slc26a4 is required to stabilize hearing in DE17.5 ears between 1 and 3months of age. We tested our hypothesis by evaluating the effect of postnatal re-induction of Slc26a4 expression on hearing. Readministration of dox to DE17.5 mice at postnatal day 6 (P6), but not at 1month of age, resulted in reduced click-evoked auditory brainstem response (ABR) thresholds, less fluctuation of hearing and a higher surface density of pendrin expression in spindle-shaped cells of the stria vascularis. Pendrin expression in spindle-shaped cells was inversely correlated with ABR thresholds. These findings suggest that stabilization of hearing by readministration of dox at P6 is mediated by pendrin expression in spindle-shaped cells. We conclude that early re-induction of Slc26a4 expression can prevent fluctuation of hearing in our Slc26a4-insufficient mouse model. Restoration of SLC26A4 expression and function could reduce or prevent fluctuation of hearing in EVA patients.

| S-EPMC4905817 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data