Early Death of 2 Siblings Related to Mutations in LMOD2, a Recently Discovered Cause of Neonatal Dilated Cardiomyopathy
Steven C. Greenway, MSc, MD, FRCPC,
Deborah Fruitman, MD, FRCPC,
Raechel Ferrier, MSc, MA, CCGC,
Cathleen Huculak, MSc, CCGC,
Julien Marcadier, MD, FRCPC,
Consolato Sergi, MD, PhD, FRCPC,
Francois P. Bernier, MD, FRCPC
Affiliations
Steven C. Greenway, MSc, MD, FRCPC
Department of Pediatrics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Sciences and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Corresponding author: Dr Steven C. Greenway, Section of Cardiology, Alberta Children's Hospital, 28 Oki Drive NW, Calgary, Alberta T3B 6A8, Canada. Tel.: +1-403-955-5049; fax: +1-403-955-7621.
Deborah Fruitman, MD, FRCPC
Department of Pediatrics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Raechel Ferrier, MSc, MA, CCGC
Section of Clinical Genetics and Metabolics, Alberta Children's Hospital, Calgary, Alberta, Canada
Cathleen Huculak, MSc, CCGC
Section of Clinical Genetics and Metabolics, Alberta Children's Hospital, Calgary, Alberta, Canada
Julien Marcadier, MD, FRCPC
Department of Pediatrics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Consolato Sergi, MD, PhD, FRCPC
Division of Anatomic Pathology, Children's Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada
Francois P. Bernier, MD, FRCPC
Department of Pediatrics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
We report a family with 2 neonatal deaths related to dilated cardiomyopathy (DCM) and compound heterozygous loss-of-function variants (c.1243_1244del, p.Leu415Valfs*108 and c.1537C > T, p.Arg513*) in Leiomodin 2 (LMOD2), a recently documented cause of early DCM. The phenotype in mice and humans consists of early, severe cardiac dilation and dysfunction related to decreased functional LMOD2, which results in abnormal actin filaments and abnormal myocardial contractility. Our cases confirm mutations in LMOD2 as a cause of DCM in humans and highlight the rapid changes occurring in cardiac genetics and the importance of reviewing previously negative genetic test results in the context of emerging literature. RÉSUMÉ: Notre compte rendu concerne une famille dont deux nouveau-nés sont décédés des suites d'une cardiomyopathie dilatée (CMD) et qui présentaient une perte hétérozygote composite de variants fonctionnels (c.1243_1244del, p.Leu415Valfs*108 et c.1537C > T, p.Arg513*) du gène Leiomodin 2 (LMOD2), une cause récemment avérée de CMD précoce. Chez la souris et l'humain, le phénotype de cette anomalie consiste en une dilatation et une dysfonction cardiaques sévères précoces liées à une diminution de la fonction du gène LMOD2 entraînant des anomalies dans les filaments d'actine et la contractilité du myocarde. Nos cas permettent de confirmer que les mutations du gène LMOD2 sont une cause de CMD chez l'humain. Ils mettent en évidence les modifications rapides se produisant dans la génétique cardiaque et l'importance de revoir les résultats négatifs d'anciens tests génétiques à la lumière des nouvelles données publiées.
