Linkage and mutation analysis in two Taiwanese families with Long QT syndrome

Yu Lin Ko, Der Yan Tai, Shih Ann Chen, Guey-Jen Lee, Chiu Hsin Chu, Ming Wei Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Long QT syndrome (LQT) is a cardiovascular disorder causing syncope and sudden death from arrhythmias. Mutations in KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A genes encoding cardiac potassium and sodium ion channels cause LQT. Two Taiwanese LQT families were screened for mutations in these ion channel genes. In family H87, the diagnosis was made in the 25-year-old female proband and six family members based on recurrent syncope and/or a prolonged QT interval. Genotyping revealed a novel nonsense mutation, R744X (C to T transition in codon 744), in the KCNH2 potassium channel gene, resulting in truncation of the putative cyclic nucleotide-binding domain and C-terminal region of the HERG K+-channel in all affected family members. The mutation was confirmed by DdeI endonuclease digestion of the DNA from each family member. The 26-year-old female proband in family L89 developed repeated syncope with QTc of 0.61 seconds. After linkage and mutation analysis, the syndrome in this family was associated with a novel KCNQ1 missense mutation, T309I, causing the substitution of a threonine residue at position 309, in the pore region of the KvLQT1 K+-channel, with an isoleucine. By Tsp45I restriction analysis, the mutation was noted in the proband and the proband's asymptomatic brother, but was not detected in 100 unrelated normal individuals. Identification of a mutation has clinical implications for presymptomatic diagnosis and therapy.

Original languageEnglish
Pages (from-to)767-771
Number of pages5
JournalJournal of the Formosan Medical Association
Volume100
Issue number11
Publication statusPublished - 2001 Dec 1

Fingerprint

Long QT Syndrome
Mutation
Syncope
Potassium Channels
Genes
Isoleucine
Sodium Channels
Nonsense Codon
Cyclic Nucleotides
Missense Mutation
Threonine
Sudden Death
Ion Channels
Codon
Cardiac Arrhythmias
Siblings
Digestion
DNA

Keywords

  • Arrhythmia
  • KCNH2
  • KCNQ1
  • Long QT syndrome
  • Potassium channel

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ko, Y. L., Tai, D. Y., Chen, S. A., Lee, G-J., Chu, C. H., & Lin, M. W. (2001). Linkage and mutation analysis in two Taiwanese families with Long QT syndrome. Journal of the Formosan Medical Association, 100(11), 767-771.

Linkage and mutation analysis in two Taiwanese families with Long QT syndrome. / Ko, Yu Lin; Tai, Der Yan; Chen, Shih Ann; Lee, Guey-Jen; Chu, Chiu Hsin; Lin, Ming Wei.

In: Journal of the Formosan Medical Association, Vol. 100, No. 11, 01.12.2001, p. 767-771.

Research output: Contribution to journalArticle

Ko, YL, Tai, DY, Chen, SA, Lee, G-J, Chu, CH & Lin, MW 2001, 'Linkage and mutation analysis in two Taiwanese families with Long QT syndrome', Journal of the Formosan Medical Association, vol. 100, no. 11, pp. 767-771.
Ko, Yu Lin ; Tai, Der Yan ; Chen, Shih Ann ; Lee, Guey-Jen ; Chu, Chiu Hsin ; Lin, Ming Wei. / Linkage and mutation analysis in two Taiwanese families with Long QT syndrome. In: Journal of the Formosan Medical Association. 2001 ; Vol. 100, No. 11. pp. 767-771.
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