Role of common and rare variants in SCN10A: Results from the Brugada syndrome QRS locus gene discovery collaborative study

Elijah R. Behr, Eleonora Savio-Galimberti, Julien Barc, Anders G. Holst, Evmorfia Petropoulou, Bram P. Prins, Javad Jabbari, Margherita Torchio, Myriam Berthet, Yuka Mizusawa, Tao Yang, Eline A. Nannenberg, Federica Dagradi, Peter Weeke, Rachel Bastiaenan, Michael J. Ackerman, Stig Haunso, Antoine Leenhardt, Stefan Kääb, Vincent ProbstRichard Redon, Sanjay Sharma, Arthur Wilde, Jacob Tfelt-Hansen, Peter Schwartz, Dan M. Roden, Connie R. Bezzina, Morten Olesen, Dawood Darbar, Pascale Guicheney, Lia Crotti, Yalda Jamshidi

Research output: Contribution to journalArticlepeer-review


Aims: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration. Methods and results: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN, CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%). Forty-nine variants were identified: 18 were rare (MAF V1.8 were performed for SCN10A common variants V1073, A1073, and rare variants of interest: A200V and I671V. V1073, A200V and I671V, demonstrated significant reductions in peak INa compared with ancestral allele A1073 (rs6795970). Conclusion: Rare variants in the screened QRS-associated genes (including SCN10A) are not responsible for a significant proportion of SCN5A mutation negative BrS. The common SNP SCN10A V1073 was strongly associated with BrS and demonstrated loss of NaV1.8 function, as did rare variants in isolated patients.

Original languageEnglish
Pages (from-to)520-529
Number of pages10
JournalCardiovascular Research
Issue number3
Publication statusPublished - Jun 1 2015


  • Brugada syndrome
  • Genetics
  • QRS duration
  • Rare variants
  • SCN10A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology


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