Torsades de Pointes electrical storm in children with KCNH2 mutations

Figures

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  Fig. 1. Clinical data of Case one : (A) ECG showed sinus bradycardia, prolonged Q-T interval (QTc = 589ms), inverted T waves in leadsII, III, aVF, and V4-V6. (B) Dynamic ECG showed Torsades de Pointes when one of the episodes occurred

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  Fig. 2. Clinical data of Case two: (A) ECG: It showed prolonged QT interval (QTc = 500ms), inverted T waves in leads II, III, aVF, and V4-V6. (B) VEEG: When the girl had a attack, no abnormal discharge was found in the synchronous monitoring VEEG, but ventricular fibrillation was observed in the synchronous monitoring ECG. (C) ECG monitor revealed RonT and TdP when multilayer suture during ICD implantation. (D) The display of pacemaker program controller: After interrogating the pacemaker, TdP was confirmed and was terminated by automatically defibrillation converting of ICD in the process of resuscitation of anesthesia

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  Fig. 3. The filtering process for WES data. (A) Case one: It contains 15,231 total coding variants. Then, 322 common variants, 54 deleterious variations, 2 genetic analyses, and final 1 associated with this phenotype variation were filtered: KCNH2(c.1841 C > T). (B) Case two: It contains 47,079 total coding variants. Then, 5, 422 common variants, 4057 deleterious variations, 5 genetic analyses, final 1 associated with this phenotype variation were filtered: KCNH2(c.1838 C > T)

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  Fig. 4. Sanger sequencing and data analysis: (A) Heterozygous variant c.1841 C > T (p.Ala614Val) in the KCNH2 gene was detected in the whole blood genomic DNA of Case one. (B) The genetic cardiac arrhythmia panel revealed a missense mutation of KCNH2 gene in Case two: c.1838 C > T (p.Thr613Met). (C) Secondary structure analysis showed that some amino acids near the mutation changed, from “α helix” to “irregular curling”, “peptide chain extension”, and from “peptide chain extension” to “irregular curling” after the p.Ala614Val missense mutation occurred. (D) Secondary structure analysis showed that some amino acids near the mutation changed from “irregular curling” and “peptide chain extension” to “α helix” and “irregular curling”, respectively, after the occurrence of missense mutation KCNH2: p.Thr613Met. (E) Three-dimensional structure analysis of protein showed that p.Ala614Val missense mutation would lead to a weakening of the interaction between amino acid residues and may affect the three-dimensional structure of the protein. (F) Protein three-dimensional structure analysis showed that after the mutation of KCNH2 gene p.Thr613Met may affect the three-dimensional structure of the…