Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Autosomal recessive postlingual hearing loss (DFNB8): compound heterozygosity for two novel TMPRSS3 mutations in German siblings.

ABSTRACT: Mutations in the transmembrane protease, serine 3 (TMPRSS3) gene, encoding a transmembrane serine protease, cause autosomal recessive deafness childhood (DFNB8) or congenital onset (DFNB10). TMPRSS3 mutations have been mainly identified in patients from Asian and Mediterranean countries and seem to be a rare finding in the Northern European population so far. The identification of two novel pathogenic TMPRSS3 mutations (c.646C-->T - R216C; c.916G-->A - A306T) is described in four affected siblings of German origin with postlingual hearing loss, treated by bilateral cochlear implantation with good results. Although TMPRSS3 mutations are supposed to be a rare cause of autosomal recessive hearing loss, in families with postlingual disease onset TMPRSS3 is the most favourable candidate gene after exclusion of GJB2 mutations.

SUBMITTER: Elbracht M

PROVIDER: S-EPMC2752172 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Autosomal recessive postlingual hearing loss (DFNB8): compound heterozygosity for two novel TMPRSS3 mutations in German siblings.

Elbracht Miriam M Senderek Jan J Eggermann Thomas T Thürmer Christian C Park Jonas J Westhofen Martin M Zerres Klaus K

Journal of medical genetics 20070601 6

Mutations in the transmembrane protease, serine 3 (TMPRSS3) gene, encoding a transmembrane serine protease, cause autosomal recessive deafness childhood (DFNB8) or congenital onset (DFNB10). TMPRSS3 mutations have been mainly identified in patients from Asian and Mediterranean countries and seem to be a rare finding in the Northern European population so far. The identification of two novel pathogenic TMPRSS3 mutations (c.646C-->T - R216C; c.916G-->A - A306T) is described in four affected siblin ...[more]

PMID: 17551081

Similar Datasets

Compound Heterozygosity for <i>OTOA</i> Truncating Variant and Genomic Rearrangement Cause Autosomal Recessive Sensorineural Hearing Loss in an Italian Family.

Project description:Hearing loss (HL) affects 1-3 newborns per 1000 and, in industrialized countries, recognizes a genetic etiology in more than 80% of the congenital cases. Excluding GJB2 and GJB6, OTOA is one of the leading genes associated with autosomal recessive non-syndromic HL. Allelic heterogeneity linked to OTOA also includes genomic rearrangements facilitated by non-allelic homologous recombination with the neighboring OTOAP1 pseudogene. We present a couple of Italian siblings affected by moderate to severe sensorineural hearing loss (SNHL) due to compound heterozygosity at the OTOA locus. Multigene panel next-generation sequencing identified the c.2223G>A, p.(Trp741*) variant transmitted from the unaffected mother. Assuming the existence of a second paternal deleterious variant which evaded detection at sequencing, genomic array analysis found a ~150 Kb microdeletion of paternal origin and spanning part of OTOA. Both deleterious alleles were identified for the first time. This study demonstrates the utility of an integrated approach to solve complex cases and allow appropriate management to affected individuals and at-risk relatives.

| S-EPMC8482239 | biostudies-literature

Identification of <i>TMPRSS3</i> as a Significant Contributor to Autosomal Recessive Hearing Loss in the Chinese Population.

Project description:Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Mutations in the TMPRSS3 (transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations in TMPRSS3 were identified in one Chinese family. To evaluate the importance of TMPRSS3 mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causative TMPRSS3 mutations, including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each of the five novel mutations was classified as severe, by both age of onset and severity of hearing loss. Together with our previous study, six families were found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine whether this mutation arose from a common ancestor, we analyzed six short tandem repeat (STR) markers spanning the TMPRSS3 gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations in TMPRSS3 account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations in SLC26A4 or GJB2 and that the recurrent TMPRSS3 mutation p.Ala306Thr is likely to be a founder mutation.

| S-EPMC5485344 | biostudies-literature

Novel TMPRSS3 variants in Pakistani families with autosomal recessive non-syndromic hearing impairment.

Project description:Mutations in the TMPRSS3 gene are known to cause autosomal recessive non-syndromic hearing impairment (ARNSHI). After undergoing a genome scan, 10 consanguineous Pakistani families with ARNSHI were found to have significant or suggestive evidence of linkage to the TMPRSS3 region. In order to elucidate if the TMPRSS3 gene is responsible for ARNSHI in these families, the gene was sequenced using DNA samples from these families. Six TMPRSS3 variants were found to cosegregate in 10 families. None of these variants were detected in 500 control chromosomes. Four novel variants, three of which are missense [c.310G>A (p.Glu104Lys), c.767C>T (p.Ala256Val) and c.1273T>C (p.Cys425Arg)] and one nonsense [c.310G>T (p.Glu104Stop)], were identified. The pathogenicity of novel missense variants was investigated through bioinformatics analyses. Additionally, the previously reported deletion c.208delC (p.His70ThrfsX19) was identified in one family and the known mutation c.1219T>C (p.Cys407Arg) was found in five families, which makes c.1219T>C (p.Cys407Arg) as the most common TMPRSS3 mutation within the Pakistani population. Identification of these novel variants lends support to the importance of elements within the low-density lipoprotein receptor A (LDLRA) and serine protease domains in structural stability, ligand binding and proteolytic activity for proper TMPRSS3 function within the inner ear.

| S-EPMC3374056 | biostudies-other

Identification of a novel homozygous mutation, TMPRSS3: c.535G>A, in a Tibetan family with autosomal recessive non-syndromic hearing loss.

Project description:Different ethnic groups have distinct mutation spectrums associated with inheritable deafness. In order to identify the mutations responsible for congenital hearing loss in the Tibetan population, mutation screening for 98 deafness-related genes by microarray and massively parallel sequencing of captured target exons was conducted in one Tibetan family with familiar hearing loss. A homozygous mutation, TMPRSS3: c.535G>A, was identified in two affected brothers. Both parents are heterozygotes and an unaffected sister carries wild type alleles. The same mutation was not detected in 101 control Tibetan individuals. This missense mutation results in an amino acid change (p.Ala179Thr) at a highly conserved site in the scavenger receptor cysteine rich (SRCR) domain of the TMPRSS3 protein, which is essential for protein-protein interactions. Thus, this mutation likely affects the interactions of this transmembrane protein with extracellular molecules. According to our bioinformatic analyses, the TMPRSS3: c.535G>A mutation might damage protein function and lead to hearing loss. These data suggest that the homozygous mutation TMPRSS3: c.535G>A causes prelingual hearing loss in this Tibetan family. This is the first TMPRSS3 mutation found in the Chinese Tibetan population.

| S-EPMC4256404 | biostudies-literature

Novel compound heterozygous MYO7A mutations in Moroccan families with autosomal recessive non-syndromic hearing loss.

Project description:The MYO7A gene encodes a protein belonging to the unconventional myosin super family. Mutations within MYO7A can lead to either non syndromic hearing loss or to the Usher syndrome type 1B (USH1B). Here, we report the results of genetic analyses performed on Moroccan families with autosomal recessive non syndromic hearing loss that identified two families with compound heterozygous MYO7A mutations. Five mutations (c.6025delG, c.6229T>A, c.3500T>A, c.5617C>T and c.4487C>A) were identified in these families, the latter presenting two differently affected branches. Multiple bioinformatics programs and molecular modelling predicted the pathogenic effect of these mutations. In conclusion, the absence of vestibular and retinal symptom in the affected patients suggests that these families have the isolated non-syndromic hearing loss DFNB2 (nonsyndromic autosomal recessive hearing loss) presentation, instead of USH1B.

| S-EPMC5417485 | biostudies-literature

Novel compound heterozygous TMC1 mutations associated with autosomal recessive hearing loss in a Chinese family.

Project description:Hereditary nonsyndromic hearing loss is highly heterogeneous and most patients with a presumed genetic etiology lack a specific diagnosis. It has been estimated that several hundred genes may be associated with this sensory deficit in humans. Here, we identified compound heterozygous mutations in the TMC1 gene as the cause of recessively inherited sensorineural hearing loss by using whole-exome sequencing in a family with two deaf siblings. Sanger sequencing confirmed that both siblings inherited a missense mutation, c.589G>A p.G197R (maternal allele), and a nonsense mutation, c.1171C>T p.Q391X (paternal allele), in TMC1. We also used DNA from 50 Chinese familial patients with ARNSHL and 208 ethnicity-matched negative samples to perform extended variants analysis. Both variants co-segregated in family 1953, which had the hearing loss phenotype, but were absent in 50 patients and 208 ethnicity-matched controls. Therefore, we concluded that the hearing loss in this family was caused by novel compound heterozygous mutations in TMC1.

| S-EPMC3653921 | biostudies-literature

Autosomal Recessive Congenital Sensorineural Hearing Loss due to a Novel Compound Heterozygous PTPRQ Mutation in a Chinese Family.

Project description:PTPRQ gene, encoding protein tyrosine phosphatase receptor Q, is essential for the normal maturation and function of hair bundle in the cochlea. Its mutations can cause the defects of stereocilia in hair cell, which lead to nonsyndromic sensorineural hearing loss. Using next-generation sequencing and Sanger sequencing method, we identified a novel compound heterozygous missense mutation, c.4472C>T p.T1491M (maternal allele) and c.1973T>C p.V658A (paternal allele), in PTPRQ gene. The two mutations are the first reported to be the cause of recessively inherited sensorineural hearing loss. Hearing loss levels and progression involved by PTPRQ mutations among the existing cases seem to be varied, and the relationship between genotypes and phenotypes is unclear. Our data here further prove the important role of PTPRQ in auditory function and provide more information for the further mechanism research of PTPRQ-related hearing loss.

| S-EPMC5932988 | biostudies-literature

Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing.

Project description:BACKGROUND: Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis. METHODS: By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis. RESULTS: We identified MYO15A c.IVS25+3G>A and c.8375 T>C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls. CONCLUSIONS: Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A.

| S-EPMC3828584 | biostudies-literature

Identification of Two Novel Compound Heterozygous PTPRQ Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family.

Project description:Mutations in PTPRQ are associated with deafness in humans due to defects of stereocilia in hair cells. Using whole exome sequencing, we identified responsible gene of family 1572 with autosomal recessively non-syndromic hearing loss (ARNSHL). We also used DNA from 74 familial patients with ARNSHL and 656 ethnically matched control chromosomes to perform extended variant analysis. We identified two novel compound heterozygous missense mutations, c. 3125 A>G p.D1042G (maternal allele) and c.5981 A>G p.E1994G (paternal allele), in the PTPRQ gene, as the cause of recessively inherited sensorineural hearing loss in family 1572. Both variants co-segregated with hearing loss phenotype in family 1572, but were absent in 74 familial patients. Heterozygosity for c. 3125 A>G was identified in two samples from unaffected Chinese individuals (656 chromosomes). Therefore, the hearing loss in this family was caused by two novel compound heterozygous mutations in PTPRQ.

| S-EPMC4412678 | biostudies-literature

Novel Mutations and Mutation Combinations of TMPRSS3 Cause Various Phenotypes in One Chinese Family with Autosomal Recessive Hearing Impairment.

Project description:Autosomal recessive hearing impairment with postlingual onset is rare. Exceptions are caused by mutations in the TMPRSS3 gene, which can lead to prelingual (DFNB10) as well as postlingual deafness (DFNB8). TMPRSS3 mutations can be classified as mild or severe, and the phenotype is dependent on the combination of TMPRSS3 mutations. The combination of two severe mutations leads to profound hearing impairment with a prelingual onset, whereas severe mutations in combination with milder TMPRSS3 mutations lead to a milder phenotype with postlingual onset. We characterized a Chinese family (number FH1523) with not only prelingual but also postlingual hearing impairment. Three mutations in TMPRSS3, one novel mutation c.36delC [p.(Phe13Serfs?12)], and two previously reported pathogenic mutations, c.916G>A (p.Ala306Thr) and c.316C>T (p.Arg106Cys), were identified. Compound heterozygous mutations of p.(Phe13Serfs?12) and p.Ala306Thr manifest as prelingual, profound hearing impairment in the patient (IV: 1), whereas the combination of p.Arg106Cys and p.Ala306Thr manifests as postlingual, milder hearing impairment in the patient (II: 2, II: 3, II: 5), suggesting that p.Arg106Cys mutation has a milder effect than p.(Phe13Serfs?12). We concluded that different combinations of TMPRSS3 mutations led to different hearing impairment phenotypes (DFNB8/DFNB10) in this family.

| S-EPMC5303592 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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