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J Pediatr Genet 2022; 11(04): 292-297
DOI: 10.1055/s-0041-1726471
Original Article

Massively Parallel Sequencing of 43 Arrhythmia Genes in a Selected SUDI Cohort from Cape Town

Laura Jane Heathfield 
1   Department of Pathology, Division of Forensic Medicine and Toxicology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
2   Department of Pathology, Division of Human Genetics, MRC/UCT Research Unit for Genomic and Precision Medicine, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
,
Hugh Watkins
3   Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
,
Lorna Jean Martin 
1   Department of Pathology, Division of Forensic Medicine and Toxicology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
,
Raj Ramesar
2   Department of Pathology, Division of Human Genetics, MRC/UCT Research Unit for Genomic and Precision Medicine, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
› Author Affiliations Funding This research was funded by RCUK Newton PhD Partnership award, National Health Laboratory Service Development Trust grant (GRANT004 94623), and the University of Cape Town.
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Abstract

Sudden unexpected death in infants (SUDI) is a devastating event, and unfortunately occurs frequently in developing countries. The emerging molecular autopsy has added value to post-mortem investigations, where genetic variants were able to explain the unexpected demise. Many of these variants have been found in genes involved in arrythmia pathways. The aim of this study was to sequence 43 genes previously associated with cardiac arrhythmia in a selected cohort of SUDI cases (n = 19) in South Africa. A total of 335 variants were found among the 19 infants, of which four were novel. The variants were classified as “likely pathogenic” (n = 1), “variant of unknown significance” (n = 54), “likely benign” (n = 56) or “benign” (n = 224). The likely pathogenic variant was LMNA NM_170707.2:c.1279C > T (p.Arg427Cys) and was found in a 3-week-old male infant of African ancestry. Variants in LMNA have previously been associated with dilated cardiomyopathy, with a typical age of onset in adulthood; therefore, this may be the first report in an infant. The yield of pathogenic or likely pathogenic variants in the classic genes typically associated with channelopathies and sudden death, was less in this study compared with other settings. This finding highlights the importance of population-specific research to develop a molecular autopsy which is locally relevant.

Keywords

molecular autopsy - SIDS - sudden unexpected death in infants - LMNA - South Africa - MiSeq

Supplementary Material



Publication History

Received: 23 July 2020

Accepted: 08 February 2021

Article published online:
14 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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