FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2064704787> ?p ?o ?g. }

• W2064704787 endingPage "e1258" @default.
• W2064704787 startingPage "e1258" @default.
• W2064704787 abstract "SCN5A encodes the alpha-subunit (Na(v)1.5) of the principle Na(+) channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Na(v)1.5 channel. Pharmacological targeting of mutation-altered Na(+) channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+) channel blockers flecainide and mexiletine. Our goal was to determine the Na(+) channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+) channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+) channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+) channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young." @default.
• W2064704787 created "2016-06-24" @default.
• W2064704787 creator A5000590729 @default.
• W2064704787 creator A5005388733 @default.
• W2064704787 creator A5014018047 @default.
• W2064704787 creator A5018722278 @default.
• W2064704787 creator A5019543720 @default.
• W2064704787 creator A5042362625 @default.
• W2064704787 creator A5085075737 @default.
• W2064704787 creator A5090012154 @default.
• W2064704787 date "2007-12-05" @default.
• W2064704787 modified "2023-10-16" @default.
• W2064704787 title "A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response" @default.
• W2064704787 cites W1583128097 @default.
• W2064704787 cites W1598538024 @default.
• W2064704787 cites W1970365812 @default.
• W2064704787 cites W1971625023 @default.
• W2064704787 cites W1981481531 @default.
• W2064704787 cites W1989598680 @default.
• W2064704787 cites W1989906944 @default.
• W2064704787 cites W1997322553 @default.
• W2064704787 cites W2000453414 @default.
• W2064704787 cites W2002003524 @default.
• W2064704787 cites W2008131233 @default.
• W2064704787 cites W2009908569 @default.
• W2064704787 cites W2012336532 @default.
• W2064704787 cites W2017951998 @default.
• W2064704787 cites W2019347362 @default.
• W2064704787 cites W2029490406 @default.
• W2064704787 cites W2043707154 @default.
• W2064704787 cites W2049811578 @default.
• W2064704787 cites W2055012964 @default.
• W2064704787 cites W2073709523 @default.
• W2064704787 cites W2074519955 @default.
• W2064704787 cites W2085007473 @default.
• W2064704787 cites W2085873341 @default.
• W2064704787 cites W2086383254 @default.
• W2064704787 cites W2095963943 @default.
• W2064704787 cites W2106326075 @default.
• W2064704787 cites W2108221570 @default.
• W2064704787 cites W2113415037 @default.
• W2064704787 cites W2114460071 @default.
• W2064704787 cites W2117665067 @default.
• W2064704787 cites W2120642757 @default.
• W2064704787 cites W2125571983 @default.
• W2064704787 cites W2126663982 @default.
• W2064704787 cites W2130321115 @default.
• W2064704787 cites W2143592728 @default.
• W2064704787 cites W2147066907 @default.
• W2064704787 cites W2151361417 @default.
• W2064704787 cites W2152031596 @default.
• W2064704787 cites W2172139099 @default.
• W2064704787 cites W4235924086 @default.
• W2064704787 cites W4238520735 @default.
• W2064704787 doi "https://doi.org/10.1371/journal.pone.0001258" @default.
• W2064704787 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2082660" @default.
• W2064704787 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18060054" @default.
• W2064704787 hasPublicationYear "2007" @default.
• W2064704787 type Work @default.
• W2064704787 sameAs 2064704787 @default.
• W2064704787 citedByCount "51" @default.
• W2064704787 countsByYear W20647047872012 @default.
• W2064704787 countsByYear W20647047872013 @default.
• W2064704787 countsByYear W20647047872014 @default.
• W2064704787 countsByYear W20647047872016 @default.
• W2064704787 countsByYear W20647047872017 @default.
• W2064704787 countsByYear W20647047872018 @default.
• W2064704787 countsByYear W20647047872019 @default.
• W2064704787 countsByYear W20647047872020 @default.
• W2064704787 countsByYear W20647047872021 @default.
• W2064704787 countsByYear W20647047872022 @default.
• W2064704787 crossrefType "journal-article" @default.
• W2064704787 hasAuthorship W2064704787A5000590729 @default.
• W2064704787 hasAuthorship W2064704787A5005388733 @default.
• W2064704787 hasAuthorship W2064704787A5014018047 @default.
• W2064704787 hasAuthorship W2064704787A5018722278 @default.
• W2064704787 hasAuthorship W2064704787A5019543720 @default.
• W2064704787 hasAuthorship W2064704787A5042362625 @default.
• W2064704787 hasAuthorship W2064704787A5085075737 @default.
• W2064704787 hasAuthorship W2064704787A5090012154 @default.
• W2064704787 hasBestOaLocation W20647047871 @default.
• W2064704787 hasConcept C104317684 @default.
• W2064704787 hasConcept C118441451 @default.
• W2064704787 hasConcept C126322002 @default.
• W2064704787 hasConcept C143065580 @default.
• W2064704787 hasConcept C174510640 @default.
• W2064704787 hasConcept C188997412 @default.
• W2064704787 hasConcept C2777561782 @default.
• W2064704787 hasConcept C2777989426 @default.
• W2064704787 hasConcept C2779362680 @default.
• W2064704787 hasConcept C2779703243 @default.
• W2064704787 hasConcept C2993353509 @default.
• W2064704787 hasConcept C501734568 @default.
• W2064704787 hasConcept C54355233 @default.
• W2064704787 hasConcept C71924100 @default.
• W2064704787 hasConcept C75563809 @default.
• W2064704787 hasConcept C83743174 @default.
• W2064704787 hasConcept C86803240 @default.

• next