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Case Reports
. 2015 Apr 15:185:114-6.
doi: 10.1016/j.ijcard.2015.03.130. Epub 2015 Mar 11.

Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia

Yanwei Xi  1 , Christina Honeywell  2 , Dapeng Zhang  3 , Jeremy Schwartzentruber  4 , Chandree L Beaulieu  2 , Martine Tetreault  5 , Taila Hartley  2 , Jennifer Marton  6 , Silvia M Vidal  6 , Jacek Majewski  5 , L Aravind  3 ; Care4Rare Canada Consortium; Michael Gollob  7 , Kym M Boycott  8 , Robert M Gow  9
Affiliations
Case Reports

Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia

Yanwei Xi et al. Int J Cardiol. .
No abstract available

Keywords: Exome sequencing; Junctional ectopic tachycardia; TNNI3K.

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Conflict of interest statement

Conflict of interest

The authors report no relationships that could be construed as a con-flict of interest.

Figures

Fig. 1
Fig. 1
A) Pedigree of the family with novel cardiac conduction system disease. Affected individuals are represented by black symbols. B) Electrocardiogram (ECG) from proband (IV-1) at presentation during a period of stable rhythm. The ECG shows sinus rhythm with first degree AV block, left anterior fascicular block (LAFB) and RBBB with QRS duration of 200 ms. C) Strip from Holter tape showing onset of tachycardia with AV dissociation and accelerating rate consistent with congenital junctional ectopic tachycardia (JET) (IV-2).
Fig. 2
Fig. 2
A) Sanger sequencing validation of TNNI3K (NM_015978.2:c.1615A>G; p.Thr539Ala) heterozygous variant identified by whole exome sequencing. B) Domain architecture of human TNNI3K and conservation of Thr539 position in animal lineage. C) Visualization of active site residues of human TNNI3K kinase domain together with ATP and Mg2+. Homology model was constructed using the Modeller9v11 program on the basis of four PDB templates, 3PPZ, 3KMW, 2EVA and 3BLQ, and evaluated by the ModFOLD program (score 0.81; any score >0.4 is a generally confident model). The α helices are shown in salmon, β sheets in blue, and loops in gray; catalytic residues Lys (K490) shown in red, Asp (D606) in green, Gly (G526) in light blue and gatekeeper residue Thr (T539) in dark blue; ATP in yellow and Mg2+ in purple. D) Surface view of ATP-binding pocket of human TNNI3K kinase domain in which the ATP and Mg2+ were hold by three key residues K490 in red, D606 in green and T539 in dark blue.
See this image and copyright information in PMC

References

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