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Infanticide vs. inherited cardiac arrhythmias.
Brohus, Malene; Arsov, Todor; Wallace, David A; Jensen, Helene Halkjær; Nyegaard, Mette; Crotti, Lia; Adamski, Marcin; Zhang, Yafei; Field, Matt A; Athanasopoulos, Vicki; Baró, Isabelle; Ribeiro de Oliveira-Mendes, Bárbara B; Redon, Richard; Charpentier, Flavien; Raju, Hariharan; DiSilvestre, Deborah; Wei, Jinhong; Wang, Ruiwu; Rafehi, Haloom; Kaspi, Antony; Bahlo, Melanie; Dick, Ivy E; Chen, Sui Rong Wayne; Cook, Matthew C; Vinuesa, Carola G; Overgaard, Michael Toft; Schwartz, Peter J.
Afiliação
  • Brohus M; Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, 9220 Aalborg, Denmark.
  • Arsov T; Department of Immunology and Infectious Disease, Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, 131 Garran Road, Canberra, Acton 2601, Australia.
  • Wallace DA; Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Jensen HH; Department of Immunology and Infectious Disease, Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, 131 Garran Road, Canberra, Acton 2601, Australia.
  • Nyegaard M; Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, 9220 Aalborg, Denmark.
  • Crotti L; Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
  • Adamski M; Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Via Pier Lombardo, 22, 20135 Milan, Italy.
  • Zhang Y; Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCCS, San Luca Hospital, Milan, Italy.
  • Field MA; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
  • Athanasopoulos V; Biology Teaching and Learning Centre, Research School of Biology and John Curtin School of Medical Research, The Australian National University, Canberra, Acton 2601, Australia.
  • Baró I; NGS Team, Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Acton 2601, Australia.
  • Ribeiro de Oliveira-Mendes BB; Department of Immunology and Infectious Disease, Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, 131 Garran Road, Canberra, Acton 2601, Australia.
  • Redon R; Centre for Tropical Bioinformatics and Molecular Biology, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia.
  • Charpentier F; Department of Immunology and Infectious Disease, Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, 131 Garran Road, Canberra, Acton 2601, Australia.
  • Raju H; Université de Nantes, CNRS, INSERM, L'institut du Thorax, F-44000 Nantes, France.
  • DiSilvestre D; Université de Nantes, CNRS, INSERM, L'institut du Thorax, F-44000 Nantes, France.
  • Wei J; Université de Nantes, CNRS, INSERM, L'institut du Thorax, F-44000 Nantes, France.
  • Wang R; Université de Nantes, CNRS, INSERM, L'institut du Thorax, F-44000 Nantes, France.
  • Rafehi H; Cardiology Department, Faculty of Medicine, Macquarie University, Sydney, New South Wales 2109, Australia.
  • Kaspi A; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • Bahlo M; Department of Physiology and Pharmacology, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
  • Dick IE; Department of Physiology and Pharmacology, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
  • Chen SRW; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia.
  • Cook MC; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia.
  • Vinuesa CG; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia.
  • Overgaard MT; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia.
  • Schwartz PJ; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia.
Europace ; 23(3): 441-450, 2021 03 08.
Article em En | MEDLINE | ID: mdl-33200177
AIMS: In 2003, an Australian woman was convicted by a jury of smothering and killing her four children over a 10-year period. Each child died suddenly and unexpectedly during a sleep period, at ages ranging from 19 days to 18 months. In 2019 we were asked to investigate if a genetic cause could explain the children's deaths as part of an inquiry into the mother's convictions. METHODS AND RESULTS: Whole genomes or exomes of the mother and her four children were sequenced. Functional analysis of a novel CALM2 variant was performed by measuring Ca2+-binding affinity, interaction with calcium channels and channel function. We found two children had a novel calmodulin variant (CALM2 G114R) that was inherited maternally. Three genes (CALM1-3) encode identical calmodulin proteins. A variant in the corresponding residue of CALM3 (G114W) was recently reported in a child who died suddenly at age 4 and a sibling who suffered a cardiac arrest at age 5. We show that CALM2 G114R impairs calmodulin's ability to bind calcium and regulate two pivotal calcium channels (CaV1.2 and RyR2) involved in cardiac excitation contraction coupling. The deleterious effects of G114R are similar to those produced by G114W and N98S, which are considered arrhythmogenic and cause sudden cardiac death in children. CONCLUSION: A novel functional calmodulin variant (G114R) predicted to cause idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, or mild long QT syndrome was present in two children. A fatal arrhythmic event may have been triggered by their intercurrent infections. Thus, calmodulinopathy emerges as a reasonable explanation for a natural cause of their deaths.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Taquicardia Ventricular / Infanticídio Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Taquicardia Ventricular / Infanticídio Idioma: En Ano de publicação: 2021 Tipo de documento: Article