{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:53:49Z","timestamp":1787320429358,"version":"build-2736575974"},"reference-count":43,"publisher":"Necmettin Erbakan University Press","issue":"04","funder":[{"name":"RCUK Newton PhD Partnership award, National Health Laboratory Service Development Trust grant, and University Research Office, University of Cape Town"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pediatr Genet"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2009=\u200919) in South Africa. A total of 335 variants were found among the 19 infants, of which four were novel. The variants were classified as \u201clikely pathogenic\u201d (n\u2009=\u20091), \u201cvariant of unknown significance\u201d (n\u2009=\u200954), \u201clikely benign\u201d (n\u2009=\u200956) or \u201cbenign\u201d (n\u2009=\u2009224). The likely pathogenic variant was LMNA NM_170707.2:c.1279C\u2009&gt;\u2009T (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.<\/jats:p>","DOI":"10.1055\/s-0041-1726471","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T19:51:10Z","timestamp":1618429870000},"page":"292-297","source":"Crossref","is-referenced-by-count":2,"title":["Massively Parallel Sequencing of 43 Arrhythmia Genes in a Selected SUDI Cohort from Cape Town"],"prefix":"10.53391","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-9419","authenticated-orcid":false,"given":"Laura Jane","family":"Heathfield","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Forensic Medicine and Toxicology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-7932","authenticated-orcid":false,"given":"Lorna Jean","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Forensic Medicine and Toxicology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Ramesar","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"31409","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"issue":"17","key":"ref1","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1161\/CIRCULATIONAHA.114.008720","article-title":"Global and regional patterns in cardiovascular mortality from 1990 to 2013","volume":"132","author":"G A Roth","year":"2015","journal-title":"Circulation"},{"issue":"07","key":"ref2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1001\/archinternmed.2009.38","article-title":"A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease","volume":"169","author":"A Mente","year":"2009","journal-title":"Arch Intern Med"},{"issue":"23","key":"ref3","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1161\/CIRCULATIONAHA.106.183216","article-title":"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics","volume":"115","author":"K J Jenkins","year":"2007","journal-title":"Circulation"},{"issue":"10","key":"ref4","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nrcardio.2013.108","article-title":"Genetic testing for inherited cardiac disease","volume":"10","author":"A AM Wilde","year":"2013","journal-title":"Nat Rev Cardiol"},{"issue":"07","key":"ref5","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/CIRCRESAHA.117.309345","article-title":"Arrhythmogenic cardiomyopathy","volume":"121","author":"D Corrado","year":"2017","journal-title":"Circ Res"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrcardio.2017.129","article-title":"Sudden infant death syndrome and inherited cardiac conditions","volume":"14","author":"A-E Baruteau","year":"2017","journal-title":"Nat Rev Cardiol"},{"issue":"S 01","key":"ref7","first-page":"S6","article-title":"Brugada syndrome: an electrical storm without warning","volume":"25","author":"I Ahmed","year":"2015","journal-title":"J Coll Physicians Surg Pak"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1542\/peds.114.1.234","article-title":"Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach","volume":"114","author":"H F Krous","year":"2004","journal-title":"Pediatrics"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.remle.2017.08.001","article-title":"Sudden cardiac death of arrhythmic origin: value of post-mortem genetic analysis","volume":"44","author":"O Campuzano","year":"2018","journal-title":"Spanish J Leg Med"},{"issue":"07","key":"ref11","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1161\/CIRCRESAHA.117.309711","article-title":"Classification, epidemiology, and global burden of cardiomyopathies","volume":"121","author":"W J McKenna","year":"2017","journal-title":"Circ Res"},{"issue":"02","key":"ref12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00414-016-1330-7","article-title":"Sudden infant death syndrome caused by cardiac arrhythmias: only a matter of genes encoding ion channels?","volume":"130","author":"G Sarquella-Brugada","year":"2016","journal-title":"Int J Legal Med"},{"issue":"09","key":"ref13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s11886-017-0885-3","article-title":"Genetic testing in inherited heart diseases: practical considerations for clinicians","volume":"19","author":"M Care","year":"2017","journal-title":"Curr Cardiol Rep"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-0038-1668079","article-title":"A systematic review of molecular autopsy studies in sudden infant death cases","volume":"7","author":"L J Heathfield","year":"2018","journal-title":"J Pediatr Genet"},{"issue":"09","key":"ref15","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.humpath.2013.01.024","article-title":"Postmortem review and genetic analysis in sudden infant death syndrome: an 11-year review","volume":"44","author":"A Evans","year":"2013","journal-title":"Hum Pathol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.forsciint.2014.01.014","article-title":"Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths","volume":"237","author":"D Wang","year":"2014","journal-title":"Forensic Sci Int"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ijcard.2007.05.001","article-title":"Postmortem molecular analysis of KCNQ1 and SCN5A genes in sudden unexplained death in young Australians","volume":"127","author":"A Doolan","year":"2008","journal-title":"Int J Cardiol"},{"issue":"07","key":"ref18","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/archdischild-2013-305331","article-title":"Long QT molecular autopsy in sudden infant death syndrome","volume":"99","author":"J M Glengarry","year":"2014","journal-title":"Arch Dis Child"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"148","DOI":"10.7196\/SAJCH.2020.v14i3.01720","article-title":"A 5-year retrospective analysis of infant death at Salt River Mortuary, Cape Town","volume":"14","author":"L J Heathfield","year":"2020","journal-title":"South African J Child Heal"},{"key":"ref20","volume-title":"The Inquests Act 58 of 1959","author":"Department of Justice. South Africa","year":"1959"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"M Martin","year":"2011","journal-title":"EMBnet Journal"},{"issue":"14","key":"ref23","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"16","key":"ref24","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"08","key":"ref25","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/ng.3036","article-title":"Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications","volume":"46","author":"A Rimmer","year":"2014","journal-title":"Nat Genet"},{"issue":"16","key":"ref26","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"K Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/humu.20654","article-title":"Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker","volume":"29","author":"M Wildeman","year":"2008","journal-title":"Hum Mutat"},{"issue":"11","key":"ref28","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","author":"C Kopanos","year":"2019","journal-title":"Bioinformatics"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/AOG.0b013e318200cb17","article-title":"Consent for autopsy research for unexpected death in early life","volume":"117","author":"H J Odendaal","year":"2011","journal-title":"Obstet Gynecol"},{"issue":"03","key":"ref31","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/01.gim.0000204468.85308.86","article-title":"The long QT syndrome family of cardiac ion channelopathies: a HuGE review","volume":"8","author":"S M Modell","year":"2006","journal-title":"Genet Med"},{"issue":"22","key":"ref32","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1161\/hc4601.099487","article-title":"Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization","volume":"104","author":"S Yusuf","year":"2001","journal-title":"Circulation"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10048-008-0149-x","article-title":"Association of dopamine transporter and monoamine oxidase molecular polymorphisms with sudden infant death syndrome and stillbirth: new insights into the serotonin hypothesis","volume":"10","author":"L Filonzi","year":"2009","journal-title":"Neurogenetics"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/19491034.2016.1260798","article-title":"Current insights into LMNA cardiomyopathies: existing models and missing LINCs","volume":"8","author":"D Brayson","year":"2017","journal-title":"Nucleus"},{"issue":"06","key":"ref36","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1136\/heartjnl-2017-312338","article-title":"Lamin and the heart","volume":"104","author":"G Captur","year":"2018","journal-title":"Heart"},{"issue":"06","key":"ref37","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1042\/BST20110670","article-title":"Clinical and genetic heterogeneity in laminopathies","volume":"39","author":"A T Bertrand","year":"2011","journal-title":"Biochem Soc Trans"},{"issue":"22","key":"ref38","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1212\/01.wnl.0000263138.57257.6a","article-title":"Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism?","volume":"68","author":"R Ben Yaou","year":"2007","journal-title":"Neurology"},{"issue":"09","key":"ref39","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1101\/gr.195800.115","article-title":"Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young","volume":"26","author":"D NR Methner","year":"2016","journal-title":"Genome Res"},{"issue":"04","key":"ref40","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1253\/circj.CJ-12-0995","article-title":"Novel SCN3B mutation associated with Brugada syndrome affects intracellular trafficking and function of Nav1.5","volume":"77","author":"T Ishikawa","year":"2013","journal-title":"Circ J"},{"issue":"38","key":"ref41","doi-asserted-by":"crossref","first-page":"40185","DOI":"10.1074\/jbc.M406018200","article-title":"Ankyrin-B targets \u03b22-spectrin to an intracellular compartment in neonatal cardiomyocytes","volume":"279","author":"P J Mohler","year":"2004","journal-title":"J Biol Chem"},{"issue":"06","key":"ref42","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.yjmcc.2008.08.005","article-title":"Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease","volume":"45","author":"S R Cunha","year":"2008","journal-title":"J Mol Cell Cardiol"},{"issue":"03","key":"ref43","doi-asserted-by":"crossref","first-page":"216","DOI":"10.7326\/0003-4819-149-3-200808050-00020","article-title":"Fever increases the risk for cardiac arrest in the Brugada syndrome","volume":"149","author":"A S Amin","year":"2008","journal-title":"Ann Intern Med"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000244052","article-title":"A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model","volume":"65","author":"J J Filiano","year":"1994","journal-title":"Biol Neonate"},{"issue":"10","key":"ref45","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/j.1651-2227.1998.tb01410.x","article-title":"Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome","volume":"87","author":"S H Opdal","year":"1998","journal-title":"Acta Paediatr"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fcvm.2017.00072","article-title":"Molecular autopsy for sudden death in the young: is data aggregation the key?","volume":"4","author":"M Rueda","year":"2017","journal-title":"Front Cardiovasc Med"}],"container-title":["Journal of Pediatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1726471.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T19:45:57Z","timestamp":1758138357000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1726471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,14]]},"references-count":43,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2022,10,18]]},"published-print":{"date-parts":[[2022,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1726471","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2146-4596","2146-460X"],"issn-type":[{"value":"2146-4596","type":"print"},{"value":"2146-460X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,14]]}}}