Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380448051> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W4380448051 abstract "Abstract Background and Aims Gitelman syndrome is a salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. It is caused by homozygous recessive or compound heterozygous pathogenic variants in SLC12A3, which encodes the Na+-Cl− cotransporter (NCC). In up to 10% of patients with Gitelman syndrome, current genetic techniques detect only one specific pathogenic variant. This study aimed to identify a second pathogenic variant in introns, splice sites, or promoters to increase the diagnostic yield. Method Long-read sequencing of SLC12A3 was performed in 67 DNA samples from individuals with suspected Gitelman syndrome in whom a single likely pathogenic or pathogenic variant was previously detected. In addition, we sequenced DNA samples from 28 individuals with one variant of uncertain significance or no candidate variant. Midigene splice assays assessed the pathogenicity of novel intronic variants. Results A second likely pathogenic/pathogenic variant was identified in 45 (67%) patients. Those with two likely pathogenic/pathogenic variants had a more severe electrolyte phenotype than other patients. Of the 45 patients, 16 had intronic variants outside of canonic splice sites (nine variants, mostly deep intronic, six novel), whereas 29 patients had an exonic variant or canonic splice site variant. Midigene splice assays of the previously known c.1670-191C>T variant and intronic candidate variants demonstrated aberrant splicing patterns. Conclusion Intronic pathogenic variants explain an important part of the missing heritability in Gitelman syndrome. Long-read sequencing should be considered in diagnostic workflows for Gitelman syndrome, especially in patients with one pathogenic variant." @default.
- W4380448051 created "2023-06-14" @default.
- W4380448051 creator A5005551299 @default.
- W4380448051 creator A5009728185 @default.
- W4380448051 creator A5013194806 @default.
- W4380448051 creator A5028527762 @default.
- W4380448051 creator A5043204023 @default.
- W4380448051 creator A5055846286 @default.
- W4380448051 creator A5065333129 @default.
- W4380448051 creator A5084777052 @default.
- W4380448051 creator A5089804308 @default.
- W4380448051 date "2023-06-01" @default.
- W4380448051 modified "2023-09-24" @default.
- W4380448051 title "#2568 LONG-READ SEQUENCING IDENTIFIES NOVEL PATHOGENIC INTRONIC VARIANTS IN GITELMAN SYNDROME" @default.
- W4380448051 doi "https://doi.org/10.1093/ndt/gfad063a_2568" @default.
- W4380448051 hasPublicationYear "2023" @default.
- W4380448051 type Work @default.
- W4380448051 citedByCount "0" @default.
- W4380448051 crossrefType "journal-article" @default.
- W4380448051 hasAuthorship W4380448051A5005551299 @default.
- W4380448051 hasAuthorship W4380448051A5009728185 @default.
- W4380448051 hasAuthorship W4380448051A5013194806 @default.
- W4380448051 hasAuthorship W4380448051A5028527762 @default.
- W4380448051 hasAuthorship W4380448051A5043204023 @default.
- W4380448051 hasAuthorship W4380448051A5055846286 @default.
- W4380448051 hasAuthorship W4380448051A5065333129 @default.
- W4380448051 hasAuthorship W4380448051A5084777052 @default.
- W4380448051 hasAuthorship W4380448051A5089804308 @default.
- W4380448051 hasBestOaLocation W43804480511 @default.
- W4380448051 hasConcept C104317684 @default.
- W4380448051 hasConcept C191897082 @default.
- W4380448051 hasConcept C192562407 @default.
- W4380448051 hasConcept C2776183862 @default.
- W4380448051 hasConcept C2779749707 @default.
- W4380448051 hasConcept C2780989783 @default.
- W4380448051 hasConcept C2781145326 @default.
- W4380448051 hasConcept C2994225774 @default.
- W4380448051 hasConcept C36823959 @default.
- W4380448051 hasConcept C501734568 @default.
- W4380448051 hasConcept C51679486 @default.
- W4380448051 hasConcept C543218039 @default.
- W4380448051 hasConcept C54355233 @default.
- W4380448051 hasConcept C71924100 @default.
- W4380448051 hasConcept C76818968 @default.
- W4380448051 hasConcept C86803240 @default.
- W4380448051 hasConcept C94671646 @default.
- W4380448051 hasConceptScore W4380448051C104317684 @default.
- W4380448051 hasConceptScore W4380448051C191897082 @default.
- W4380448051 hasConceptScore W4380448051C192562407 @default.
- W4380448051 hasConceptScore W4380448051C2776183862 @default.
- W4380448051 hasConceptScore W4380448051C2779749707 @default.
- W4380448051 hasConceptScore W4380448051C2780989783 @default.
- W4380448051 hasConceptScore W4380448051C2781145326 @default.
- W4380448051 hasConceptScore W4380448051C2994225774 @default.
- W4380448051 hasConceptScore W4380448051C36823959 @default.
- W4380448051 hasConceptScore W4380448051C501734568 @default.
- W4380448051 hasConceptScore W4380448051C51679486 @default.
- W4380448051 hasConceptScore W4380448051C543218039 @default.
- W4380448051 hasConceptScore W4380448051C54355233 @default.
- W4380448051 hasConceptScore W4380448051C71924100 @default.
- W4380448051 hasConceptScore W4380448051C76818968 @default.
- W4380448051 hasConceptScore W4380448051C86803240 @default.
- W4380448051 hasConceptScore W4380448051C94671646 @default.
- W4380448051 hasIssue "Supplement_1" @default.
- W4380448051 hasLocation W43804480511 @default.
- W4380448051 hasOpenAccess W4380448051 @default.
- W4380448051 hasPrimaryLocation W43804480511 @default.
- W4380448051 hasRelatedWork W2005170530 @default.
- W4380448051 hasRelatedWork W2005356917 @default.
- W4380448051 hasRelatedWork W2039352533 @default.
- W4380448051 hasRelatedWork W2059232697 @default.
- W4380448051 hasRelatedWork W2066476772 @default.
- W4380448051 hasRelatedWork W2092554027 @default.
- W4380448051 hasRelatedWork W2127670549 @default.
- W4380448051 hasRelatedWork W2613432108 @default.
- W4380448051 hasRelatedWork W4242521457 @default.
- W4380448051 hasRelatedWork W4309990826 @default.
- W4380448051 hasVolume "38" @default.
- W4380448051 isParatext "false" @default.
- W4380448051 isRetracted "false" @default.
- W4380448051 workType "article" @default.