FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2050795637> ?p ?o ?g. }

• W2050795637 endingPage "326" @default.
• W2050795637 startingPage "319" @default.
• W2050795637 abstract "Mutations in the <i>SLC26A4</i> gene, which encodes pendrin, cause congenital hearing loss as a manifestation of Pendred syndrome (PS) with an iodide organification defect or nonsyndromic enlarged vestibular aqueduct (NSEVA, DFNB4). There have been reports of differences between PS and NSEVA, including their auditory phenotypes and molecular genetic bases. For appropriate genetic diagnosis and counseling, it is important to functionally characterize <i>SLC26A4</i> variants. In this study, we identified and evaluated a novel null mutation of <i>SLC26A4</i> and report our method of assessing the pathogenic potential of mutations in <i>SLC26A4</i>, one of the most frequent causative genes of deafness in humans. A 3-year-old female with progressive sensorineural hearing loss and her parents were recruited. They underwent clinical, audiological, radiological and genetic evaluations, which revealed that the female patient had an enlarged vestibular aqueduct and an incomplete partition type II anomaly in the cochlea bilaterally. Sanger sequencing of the <i>SLC26A4</i> gene was also performed. For a confirmatory genetic diagnosis, we first characterized the anion/base exchange ability of mutant pendrin products in HEK 293 cells and, if necessary, evaluated whether the mutant pendrin traffics to the plasma membrane in COS-7 cells. We also expressed a null function mutant, p.H723R, and a previously documented polymorphism, p.P542R, as controls. The pure tone average was 66 dB HL in the right ear and 75 dB HL in the left ear. Sequencing of <i>SLC26A4</i> revealed a known pathogenic mutation (p.H723R) and a novel missense variant (p.V510D) as a compound heterozygote. When we expressed the p.V510D mutant pendrin in mammalian cells, the rate constants for Cl^-/HCO₃^- exchange were 10.96 ± 4.79% compared with those of wild-type pendrin. This figure was comparable to that of p.H723R, indicating p.V510D to be another pathogenic mutation with a null function. The p.V510D pendrin product was shown to be entrapped in the endoplasmic reticulum (ER) at 24-30 h after transfection, and not trafficked to the plasma membrane in COS-7 cells, suggesting retention in the ER and abnormal trafficking as the pathogenic mechanism. This was similar to p.H723R, which is a null function founder mutant in this population but is a candidate variant for future drug therapy to rescue the abnormal cell trafficking. Impaired cellular trafficking due to ER retention and abolished exchange activity of the newly detected p.V510D indicates the pathogenic potential of this variant. These missense variants may be good candidate variants for drug therapy if the intrinsic exchange activity is not damaged by the change." @default.
• W2050795637 created "2016-06-24" @default.
• W2050795637 creator A5011007448 @default.
• W2050795637 creator A5027428648 @default.
• W2050795637 creator A5027435828 @default.
• W2050795637 creator A5029057202 @default.
• W2050795637 creator A5044912860 @default.
• W2050795637 creator A5061799496 @default.
• W2050795637 creator A5081345276 @default.
• W2050795637 creator A5083812385 @default.
• W2050795637 creator A5083973246 @default.
• W2050795637 date "2014-01-01" @default.
• W2050795637 modified "2023-10-18" @default.
• W2050795637 title "Identification of Novel Functional Null Allele of <b><i>SLC26A4</i></b> Associated with Enlarged Vestibular Aqueduct and Its Possible Implication" @default.
• W2050795637 cites W1964313556 @default.
• W2050795637 cites W1975670010 @default.
• W2050795637 cites W1984535376 @default.
• W2050795637 cites W2000323225 @default.
• W2050795637 cites W2008973531 @default.
• W2050795637 cites W2023471002 @default.
• W2050795637 cites W2037454945 @default.
• W2050795637 cites W2041838113 @default.
• W2050795637 cites W2051452646 @default.
• W2050795637 cites W2053606850 @default.
• W2050795637 cites W2055144172 @default.
• W2050795637 cites W2058677398 @default.
• W2050795637 cites W2065804137 @default.
• W2050795637 cites W2082372749 @default.
• W2050795637 cites W2096996940 @default.
• W2050795637 cites W2097880791 @default.
• W2050795637 cites W2101617815 @default.
• W2050795637 cites W2102180389 @default.
• W2050795637 cites W2106323764 @default.
• W2050795637 cites W2116391207 @default.
• W2050795637 cites W2145979704 @default.
• W2050795637 cites W2151236920 @default.
• W2050795637 cites W2153767327 @default.
• W2050795637 cites W2162371082 @default.
• W2050795637 cites W2165643671 @default.
• W2050795637 cites W4254652840 @default.
• W2050795637 doi "https://doi.org/10.1159/000366190" @default.
• W2050795637 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25358692" @default.
• W2050795637 hasPublicationYear "2014" @default.
• W2050795637 type Work @default.
• W2050795637 sameAs 2050795637 @default.
• W2050795637 citedByCount "12" @default.
• W2050795637 countsByYear W20507956372015 @default.
• W2050795637 countsByYear W20507956372016 @default.
• W2050795637 countsByYear W20507956372017 @default.
• W2050795637 countsByYear W20507956372018 @default.
• W2050795637 countsByYear W20507956372019 @default.
• W2050795637 countsByYear W20507956372021 @default.
• W2050795637 countsByYear W20507956372022 @default.
• W2050795637 crossrefType "journal-article" @default.
• W2050795637 hasAuthorship W2050795637A5011007448 @default.
• W2050795637 hasAuthorship W2050795637A5027428648 @default.
• W2050795637 hasAuthorship W2050795637A5027435828 @default.
• W2050795637 hasAuthorship W2050795637A5029057202 @default.
• W2050795637 hasAuthorship W2050795637A5044912860 @default.
• W2050795637 hasAuthorship W2050795637A5061799496 @default.
• W2050795637 hasAuthorship W2050795637A5081345276 @default.
• W2050795637 hasAuthorship W2050795637A5083812385 @default.
• W2050795637 hasAuthorship W2050795637A5083973246 @default.
• W2050795637 hasConcept C104317684 @default.
• W2050795637 hasConcept C143065580 @default.
• W2050795637 hasConcept C149011108 @default.
• W2050795637 hasConcept C190041318 @default.
• W2050795637 hasConcept C2776685072 @default.
• W2050795637 hasConcept C2777399954 @default.
• W2050795637 hasConcept C2780130748 @default.
• W2050795637 hasConcept C501734568 @default.
• W2050795637 hasConcept C54355233 @default.
• W2050795637 hasConcept C548259974 @default.
• W2050795637 hasConcept C71924100 @default.
• W2050795637 hasConcept C76818968 @default.
• W2050795637 hasConcept C86803240 @default.
• W2050795637 hasConceptScore W2050795637C104317684 @default.
• W2050795637 hasConceptScore W2050795637C143065580 @default.
• W2050795637 hasConceptScore W2050795637C149011108 @default.
• W2050795637 hasConceptScore W2050795637C190041318 @default.
• W2050795637 hasConceptScore W2050795637C2776685072 @default.
• W2050795637 hasConceptScore W2050795637C2777399954 @default.
• W2050795637 hasConceptScore W2050795637C2780130748 @default.
• W2050795637 hasConceptScore W2050795637C501734568 @default.
• W2050795637 hasConceptScore W2050795637C54355233 @default.
• W2050795637 hasConceptScore W2050795637C548259974 @default.
• W2050795637 hasConceptScore W2050795637C71924100 @default.
• W2050795637 hasConceptScore W2050795637C76818968 @default.
• W2050795637 hasConceptScore W2050795637C86803240 @default.
• W2050795637 hasIssue "5" @default.
• W2050795637 hasLocation W20507956371 @default.
• W2050795637 hasLocation W20507956372 @default.
• W2050795637 hasOpenAccess W2050795637 @default.
• W2050795637 hasPrimaryLocation W20507956371 @default.
• W2050795637 hasRelatedWork W101124211 @default.
• W2050795637 hasRelatedWork W1998983519 @default.
• W2050795637 hasRelatedWork W2056204692 @default.
• W2050795637 hasRelatedWork W2117110650 @default.

• next