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. 2016:2016:3684965.
doi: 10.1155/2016/3684965. Epub 2016 Nov 28.

Exome Sequencing Identifies Compound Heterozygous Mutations in SCN5A Associated with Congenital Complete Heart Block in the Thai Population

Chuphong Thongnak  1 , Pornprot Limprasert  2 , Duangkamol Tangviriyapaiboon  3 , Suchaya Silvilairat  4 , Apichaya Puangpetch  5 , Ekawat Pasomsub  6 , Chonlaphat Sukasem  5 , Wasun Chantratita  6
Affiliations

Exome Sequencing Identifies Compound Heterozygous Mutations in SCN5A Associated with Congenital Complete Heart Block in the Thai Population

Chuphong Thongnak et al. Dis Markers. 2016.

Abstract

Background. Congenital heart block is characterized by blockage of electrical impulses from the atrioventricular node (AV node) to the ventricles. This blockage can be caused by ion channel impairment that is the result of genetic variation. This study aimed to investigate the possible causative variants in a Thai family with complete heart block by using whole exome sequencing. Methods. Genomic DNA was collected from a family consisting of five family members in three generations in which one of three children in generation III had complete heart block. Whole exome sequencing was performed on one complete heart block affected child and one unaffected sibling. Bioinformatics was used to identify annotated and filtered variants. Candidate variants were validated and the segregation analysis of other family members was performed. Results. This study identified compound heterozygous variants, c.101G>A and c.3832G>A, in the SCN5A gene and c.28730C>T in the TTN gene. Conclusions. Compound heterozygous variants in the SCN5A gene were found in the complete heart block affected child but these two variants were found only in the this affected sibling and were not found in other unaffected family members. Hence, these variants in the SCN5A gene were the most possible disease-causing variants in this family.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvements with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Figures

Figure 1
Figure 1
Electrocardiography of index case (III-2) shows third-degree atrioventricular block, atrial rate 100/min, ventricular rate 49/min, and ventricular pacing spikes before some QRS complexes.
Figure 2
Figure 2
The lineage of the family with complete heart block indicated by the dark symbol, females by circles, and males by squares. Letters (a) and (b) indicate genotypes of 2 variants in the SCN5A gene for c.101G>A and c.3832G>A. The homozygous reference genotypes are indicated by (−/−) and heterozygous alternate genotypes by (−/+). The genotypes of II-1 are presumed genotypes which are inferred from his children.
Figure 3
Figure 3
Filtering procedure of variants obtained by whole exome sequencing 2nd data analysis.
Figure 4
Figure 4
Chromatograms of 2 heterozygous missense variants in SCN5A gene: c.101G>A (a) and c.3832G>A (b). Letters in [] indicate complementary (FWD) alleles.
Figure 5
Figure 5
Schematic of the transmembrane topology of the SCN5A protein. The location of the variants R34H (c.101G>A) and V1278I (c.3832G>A) is shown.
See this image and copyright information in PMC

References

    1. Friedman D. M., Duncanson L. J., Glickstein J., Buyon J. P. A review of congenital heart block. Images in Paediatric Cardiology. 2003;5(3):36–48. - PMC - PubMed
    1. Smits J. P., Veldkamp M. W., Wilde A. A. Mechanisms of inherited cardiac conduction disease. Europace. 2005;7(2):122–137. - PubMed
    1. Schwartz P. J., Garson A., Jr., Paul T., et al. Guidelines for the interpretation of the neonatal electrocardiogram: a Task Force of the European Society of Cardiology. European Heart Journal. 2002;23(17):1329–1344. doi: 10.1053/euhj.2002.3274. - DOI - PubMed
    1. Park D. S., Fishman G. I. The cardiac conduction system. Circulation. 2011;123(8):904–915. doi: 10.1161/CIRCULATIONAHA.110.942284. - DOI - PMC - PubMed
    1. Ueda K., Nakamura K., Hayashi T., et al. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. The Journal of Biological Chemistry. 2004;279(26):27194–27198. doi: 10.1074/jbc.m311953200. - DOI - PubMed

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