Open AccessMassively Parallel Sequencing of 43 Arrhythmia Genes in a Selected SUDI Cohort from Cape Town
Author(s) -
Laura Jane Heathfield,
Hugh Watkins,
Lorna J. Martin,
Raj Ramesar
Publication year - 2021
Publication title -
journal of pediatric genetics
Language(s) - English
Resource type - Journals
eISSN - 2146-4596
pISSN - 2146-460X
DOI - 10.1055/s-0041-1726471
Subject(s) - lmna , massive parallel sequencing , cohort , autopsy , medicine , sudden death , pediatrics , population , sudden cardiac death , exome sequencing , genetics , biology , gene , phenotype , dna sequencing , environmental health
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.