Sodium channel abnormalities are infrequent in patients with long QT syndrome: Identification of two novel SCN5A mutations

Duangrurdee Wattanasirichaigoon, Mark R. Vesely, Priya Duggal, Jami C. Levine, Elizabeth D. Blume, Grace S. Wolff, Sam B. Edwards, Alan H. Beggs

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Long QT syndrome (LQTS) is a heterogeneous disorder caused by mutations of at least five different loci. Three of these, LQT1, LQT2, and LQT5, encode potassium channel subunits. LQT3 encodes the cardiac-specific sodium channel, SCN5A. Previously reported LQTS-associated mutations of SCN5A include a recurring three amino acid deletion (ΔKPQ1505-1507) in four different families, and four different missense mutations. We have examined the SCN5A gene in 88 index cases with LQTS, including four with Jervell and Lange- Nielsen syndrome and the remainder with Romano-Ward syndrome. Screening portions of DIII-DIV, where mutations have previously been found, showed that none of these patients has the three amino acid deletion, ΔKPQ1505-1507, or the other four known mutations. We identified a novel missense mutation, T1645M, in the DIV; S4 voltage sensor immediately adjacent to the previously reported mutation R1644H. We also examined all of the additional pore-forming regions and voltage-sensing regions and discovered another novel mutation, T1304M, at the voltage-sensing region DIII; S4. Neither T1645M nor T1304M were seen in a panel of unaffected control individuals. Five of six T1304M gene carriers were symptomatic. In contrast to previous studies, QT(onset-c) was not a sensitive indicator of SCN5A-associated LQTS, at least in this family. These data suggest that mutations of SCN5A are responsible for only a small proportion of LQTS cases.

Original languageEnglish (US)
Pages (from-to)470-476
Number of pages7
JournalAmerican journal of medical genetics
Issue number5
StatePublished - Oct 29 1999
Externally publishedYes


  • Arrhythmia
  • Gene mutations
  • Long QT syndrome
  • Sodium channel

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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