ArticleHeart rhythm2009
Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
Article in Heart rhythm, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers.
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231 citing papers in PubMed, 466 citations in OpenAlex.
- The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients.PloS one · 2013Trial
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- NS1643 enhances the activity of T1019PfsX38 and Q1070X hERG channels associated with long QT syndrome type 2.Pflugers Archiv : European journal of physiology · 2026Article
- Congenital Long QT Syndrome: From Conventional Management to Emerging Biological Therapies.Reviews in cardiovascular medicine · 2026Review
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- Allosteric Mechanisms Underlying Long QT Syndrome Type 2 (LQT2)-Associated Mutations in hERG Channels.bioRxiv : the preprint server for biology · 2026Article
- Personalized in vitro models reveal functional impact of aHeart rhythm O2 · 2026Article
- Clinical Spectrum of Arrhythmogenic Entities in Spanish Children Carrying DeleteriousInternational journal of molecular sciences · 2026Article
- Mapping the Functional Landscape ofmedRxiv : the preprint server for health sciences · 2025Article
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- Proteome-wide model for human disease genetics.Nature genetics · 2025Article
- Investigating the role of the I-II linker in Nav1.5 channel function.The Journal of general physiology · 2025Article
- Electrophysiological characterization of the state-dependent inhibition of Kv7.1 and IMolecular pharmacology · 2025Article
- KCNH2-L693P Causes Long QT Syndrome Type 2 Through hERG Channel Dysfunction: Functional Validation of a Variant of Uncertain Significance.Molecular genetics & genomic medicine · 2025Article
- A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.Nature communications · 2025Article
- Article
- A New High Penetrant Intronic Pathogenic Variant Related to Long QT Syndrome Type 2.Journal of clinical medicine · 2025Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Structural basis of human NaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular insights into the rescue mechanism of an HERG activator against severe LQT2 mutations.Journal of biomedical science · 2025Article
171 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundLong QT syndrome (LQTS) is a potentially lethal, highly treatable cardiac channelopathy for which genetic testing has matured from discovery to translation and now clinical implementation.
objectivesHere we examine the spectrum and prevalence of mutations found in the first 2,500 unrelated cases referred for the FAMILION LQTS clinical genetic test.
methodsRetrospective analysis of the first 2,500 cases (1,515 female patients, average age at testing 23 +/- 17 years, range 0 to 90 years) scanned for mutations in 5 of the LQTS-susceptibility genes: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6).
resultsOverall, 903 referral cases (36%) hosted a possible LQTS-causing mutation that was absent in >2,600 reference alleles; 821 (91%) of the mutation-positive cases had single genotypes, whereas the remaining 82 patients (9%) had >1 mutation in > or =1 gene, including 52 cases that were compound heterozygous with mutations in >1 gene. Of the 562 distinct mutations, 394 (70%) were missense, 428 (76%) were seen once, and 336 (60%) are novel, including 92 of 199 in KCNQ1, 159 of 226 in KCNH2, and 70 of 110 in SCN5A.
conclusionThis cohort increases the publicly available compendium of putative LQTS-associated mutations by >50%, and approximately one-third of the most recently detected mutations continue to be novel. Although control population data suggest that the great majority of these mutations are pathogenic, expert interpretation of genetic test results will remain critical for effective clinical use of LQTS genetic test results.
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