Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome
Abstract Objectives Long QT syndrome (LQTS) is one of the primary causes of sudden cardiac death (SCD) in youth. Studies have identified mutations in ion channel genes as key players in the pathogenesis of LQTS. However, the specific etiology in individual families remains unknown. Methods Three unr...
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| Format: | Article |
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BMC
2023-08-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-023-03417-2 |
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| author | Nongnong Zhao Zhengyang Yu Zhejun Cai Wenai Chen Xiaopeng He Zhaoxia Huo Xiaoping Lin |
| author_facet | Nongnong Zhao Zhengyang Yu Zhejun Cai Wenai Chen Xiaopeng He Zhaoxia Huo Xiaoping Lin |
| author_sort | Nongnong Zhao |
| collection | DOAJ |
| description | Abstract Objectives Long QT syndrome (LQTS) is one of the primary causes of sudden cardiac death (SCD) in youth. Studies have identified mutations in ion channel genes as key players in the pathogenesis of LQTS. However, the specific etiology in individual families remains unknown. Methods Three unrelated Chinese pedigrees diagnosed with LQTS or Jervell and Lange-Nielsen syndrome (JLNS) were recruited clinically. Whole exome sequencing (WES) was performed and further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Results All of the probands in our study experienced syncope episodes and featured typically prolonged QTc-intervals. Two probands also presented with congenital hearing loss and iron-deficiency anemia and thus were diagnosed with JLNS. A total of five different variants in KCNQ1, encoding a subunit of the voltage-gated potassium channel, were identified in 3 probands. The heterozygous variants, KCNQ1 c.749T > C was responsible for LQTS in Case 1, transmitting in an autosomal dominant pattern. Two patterns of compound heterozygous variants were responsible for JLNS, including a large deletion causing loss of the exon 16 and missense variant c.1663 C > T in Case 2, and splicing variant c.605-2 A > G and frame-shift variant c.1265del in Case 3. To our knowledge, the compound heterozygous mutations containing a large deletion and missense variant were first reported in patients with JLNS. Conclusion Our study expanded the LQTS genetic spectrum, thus favoring disease screening and diagnosis, personalized treatment, and genetic consultation. |
| first_indexed | 2024-03-10T22:20:10Z |
| format | Article |
| id | doaj.art-3ec6d602619d480587115e5323497c66 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-03-10T22:20:10Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-3ec6d602619d480587115e5323497c662023-11-19T12:18:17ZengBMCBMC Cardiovascular Disorders1471-22612023-08-012311910.1186/s12872-023-03417-2Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndromeNongnong Zhao0Zhengyang Yu1Zhejun Cai2Wenai Chen3Xiaopeng He4Zhaoxia Huo5Xiaoping Lin6Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology, Second Affiliated Hospital, Zhejiang University School of MedicineExperimental Teaching Center, School of Basic Medical Sciences, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, Zhejiang University School of MedicineAbstract Objectives Long QT syndrome (LQTS) is one of the primary causes of sudden cardiac death (SCD) in youth. Studies have identified mutations in ion channel genes as key players in the pathogenesis of LQTS. However, the specific etiology in individual families remains unknown. Methods Three unrelated Chinese pedigrees diagnosed with LQTS or Jervell and Lange-Nielsen syndrome (JLNS) were recruited clinically. Whole exome sequencing (WES) was performed and further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Results All of the probands in our study experienced syncope episodes and featured typically prolonged QTc-intervals. Two probands also presented with congenital hearing loss and iron-deficiency anemia and thus were diagnosed with JLNS. A total of five different variants in KCNQ1, encoding a subunit of the voltage-gated potassium channel, were identified in 3 probands. The heterozygous variants, KCNQ1 c.749T > C was responsible for LQTS in Case 1, transmitting in an autosomal dominant pattern. Two patterns of compound heterozygous variants were responsible for JLNS, including a large deletion causing loss of the exon 16 and missense variant c.1663 C > T in Case 2, and splicing variant c.605-2 A > G and frame-shift variant c.1265del in Case 3. To our knowledge, the compound heterozygous mutations containing a large deletion and missense variant were first reported in patients with JLNS. Conclusion Our study expanded the LQTS genetic spectrum, thus favoring disease screening and diagnosis, personalized treatment, and genetic consultation.https://doi.org/10.1186/s12872-023-03417-2Jervell and Lange-Nielsen SyndromeLong QT syndromeGenetic variantsKCNQ1Compound heterozygosity |
| spellingShingle | Nongnong Zhao Zhengyang Yu Zhejun Cai Wenai Chen Xiaopeng He Zhaoxia Huo Xiaoping Lin Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome BMC Cardiovascular Disorders Jervell and Lange-Nielsen Syndrome Long QT syndrome Genetic variants KCNQ1 Compound heterozygosity |
| title | Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome |
| title_full | Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome |
| title_fullStr | Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome |
| title_full_unstemmed | Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome |
| title_short | Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome |
| title_sort | novel combinations of variations in kcnq1 were associated with patients with long qt syndrome or jervell and lange nielsen syndrome |
| topic | Jervell and Lange-Nielsen Syndrome Long QT syndrome Genetic variants KCNQ1 Compound heterozygosity |
| url | https://doi.org/10.1186/s12872-023-03417-2 |
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