Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/20226894http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20226894http://www.w3.org/2000/01/rdf-schema#comment"

Background

Approximately 10% of sudden infant death syndrome (SIDS) cases may stem from potentially lethal cardiac channelopathies, with approximately half of channelopathic SIDS involving the Na(V)1.5 cardiac sodium channel. Recently, Na(V) beta subunits have been implicated in various cardiac arrhythmias. Thus, the 4 genes encoding Na(V) beta subunits represent plausible candidate genes for SIDS.

Objective

This study sought to determine the spectrum, prevalence, and functional consequences of sodium channel beta-subunit mutations in a SIDS cohort.

Methods

In this institutional review board-approved study, mutational analysis of the 4 beta-subunit genes, SCN1B to 4B, was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing of DNA derived from 292 SIDS cases. Engineered mutations were coexpressed with SCN5A in HEK 293 cells and were whole-cell patch clamped. One of the putative SIDS-associated mutations was similarly studied in adenovirally transduced adult rat ventricular myocytes.

Results

Three rare (absent in 200 to 800 reference alleles) missense mutations (beta3-V36M, beta3-V54G, and beta4-S206L) were identified in 3 of 292 SIDS cases. Compared with SCN5A+beta3-WT, beta3-V36M significantly decreased peak I(Na) and increased late I(Na), whereas beta3-V54G resulted in a marked loss of function. beta4-S206L accentuated late I(Na) and positively shifted the midpoint of inactivation compared with SCN5A+beta4-WT. In native cardiomyocytes, beta4-S206L accentuated late I(Na) and increased the ventricular action potential duration compared with beta4-WT.

Conclusion

This study provides the first molecular and functional evidence to implicate the Na(V) beta subunits in SIDS pathogenesis. Altered Na(V)1.5 sodium channel function due to beta-subunit mutations may account for the molecular pathogenic mechanism underlying approximately 1% of SIDS cases."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.org/dc/terms/identifier"doi:10.1016/j.hrthm.2010.01.032"xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Tan B.H."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Ackerman M.J."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Tester D.J."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Valdivia C.R."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Makielski J.C."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Van Norstrand D.W."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Medeiros-Domingo A."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/author"Pundi K.N."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/name"Heart Rhythm"xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/pages"771-778"xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/title"Sudden infant death syndrome-associated mutations in the sodium channel beta subunits."xsd:string
http://purl.uniprot.org/citations/20226894http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/20226894http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20226894
http://purl.uniprot.org/citations/20226894http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20226894
http://purl.uniprot.org/uniprot/Q9NY72#attribution-52E21F2C6B5B0546E9AD2CA214FB681Chttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20226894
http://purl.uniprot.org/uniprot/Q8IWT1#attribution-52E21F2C6B5B0546E9AD2CA214FB681Chttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20226894
http://purl.uniprot.org/uniprot/#_A0A1W2PR05-mappedCitation-20226894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20226894
http://purl.uniprot.org/uniprot/#_B0YJ93-mappedCitation-20226894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20226894
http://purl.uniprot.org/uniprot/#_B4DI92-mappedCitation-20226894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20226894
http://purl.uniprot.org/uniprot/#_Q2KHR9-mappedCitation-20226894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20226894
http://purl.uniprot.org/uniprot/#_O60939-mappedCitation-20226894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20226894
▶