PMC4839566_01
Clinical images of both cases.. A: Pedigree analysis, ECG and 24-hour Holter analysis of the deceased 7-year-old male proband, with sinus bradycardia on the ECG, 432 ms QTc interval and extrasystolic ventricular bigeminy on the Holter-ECG. B: Pedigree analysis, epinephrine test and record of ventricular fibrillation during cardiac arrest of the 4-year-old female patient who survived. Note the prolonged 36 ms absolute QT interval after the dose of adrenaline.
pone.0153851.g001.jpg
PMC4839566_02_pone.0153851.g001.jpg
pone.0153851.g001
Because the results of the conventional tests were normal, an epinephrine test was performed (Table 1, Fig 1B and S1 Fig).
View of the p.Asn98Ser mutation.. A. Schematic view of the CALM2 gene. The red line marks the approximate location of the mutation. B. Correlation with the cDNA. The affected codon is shown in a square. C. Electropherogram of the patient showing the A>G substitution D. Protein alignments showing the Asn98 conservation across species. E. CALM2 protein sequence. Exons are shown in alternate black/blue colours. EF-hand motifs are shown in bold and underlined. Asn98 are shown in red. Note the location of the mutation at the third EF-hand motif.
pone.0153851.g002.jpg
PMC4839566_03_pone.0153851.g002.jpg
pone.0153851.g002
The variant is located at the EF-hand 3 domain, a calcium binding region. p.Asn98Ser affects a highly conserved amino acid and produces a change from a polar non-charged amino acid to another non-charged one (Fig 2).
PMC4839566_02
Clinical images of both cases.. A: Pedigree analysis, ECG and 24-hour Holter analysis of the deceased 7-year-old male proband, with sinus bradycardia on the ECG, 432 ms QTc interval and extrasystolic ventricular bigeminy on the Holter-ECG. B: Pedigree analysis, epinephrine test and record of ventricular fibrillation during cardiac arrest of the 4-year-old female patient who survived. Note the prolonged 36 ms absolute QT interval after the dose of adrenaline.
pone.0153851.g001.jpg
PMC4839566_02_pone.0153851.g001.jpg
pone.0153851.g001
Because the results of the conventional tests were normal, an epinephrine test was performed (Table 1, Fig 1B and S1 Fig).
PMC4839566_03
View of the p.Asn98Ser mutation.. A. Schematic view of the CALM2 gene. The red line marks the approximate location of the mutation. B. Correlation with the cDNA. The affected codon is shown in a square. C. Electropherogram of the patient showing the A>G substitution D. Protein alignments showing the Asn98 conservation across species. E. CALM2 protein sequence. Exons are shown in alternate black/blue colours. EF-hand motifs are shown in bold and underlined. Asn98 are shown in red. Note the location of the mutation at the third EF-hand motif.
pone.0153851.g002.jpg
PMC4839566_03_pone.0153851.g002.jpg
pone.0153851.g002
The variant is located at the EF-hand 3 domain, a calcium binding region. p.Asn98Ser affects a highly conserved amino acid and produces a change from a polar non-charged amino acid to another non-charged one (Fig 2).