title: Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction.
abstract: Left ventricular noncompaction cardiomyopathy (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. A NGS workflow, based on a panel of 95 genes developed for sequencing most prevalent sudden cardiac death-causing genes, was used to make a rapid and costless molecular diagnosis in two siblings with a severe noncompaction cardiomyopathy starting prenatally and leading to rapid cardiac failure. For the first time, a total homozygous PKP2 deletion was identified. This molecular defect was further confirmed by MLPA and array-comparative genomic hybridization (CGH). Heterozygous PKP2 mutations are usually reported in a significant proportion of Arrhythmogenic Right Ventricular Cardiomyopathy cases. Our results show, for the first time, the involvement of PKP2 in severe cardiomyopathy with ventricular non compaction.
authors.affiliation: Genetics Department, CHU-Hôpital Nord, Saint-Etienne, France.
authors.forename: F
authors.initials: F
authors.lastname: Ramond
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Hospices Civils de Lyon, Lyon, France.|NGS sequencing platform for molecular diagnosis, Hospices Civils de Lyon, Lyon, France.|Université de Lyon, Lyon, F-69003, France.|Université Lyon 1, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Janin
authors.affiliation: Paediatric Cardiology and Congenital Heart Disease Department, Cardiovascular Louis-Pradel Hospital, Hospices Civils de Lyon, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Di Filippo
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Hospices Civils de Lyon, Lyon, France.|NGS sequencing platform for molecular diagnosis, Hospices Civils de Lyon, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Chanavat
authors.affiliation: Department of Pathology, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Chalabreysse
authors.affiliation: Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, INSERM U836, UJF, Grenoble, France.|CHU de Grenoble, Laboratoire de Biochimie Génétique et Moléculaire, Grenoble, France.
authors.forename: N
authors.initials: N
authors.lastname: Roux-Buisson
authors.affiliation: Cytogenetics, Hospices Civils de Lyon, & Centre de Recherche en Neurosciences de Lyon, Equipe GENDEV, INSERM U1028; CNRS UMR5292; UCBL1, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Sanlaville
authors.affiliation: Genetics Department, CHU-Hôpital Nord, Saint-Etienne, France.
authors.forename: R
authors.initials: R
authors.lastname: Touraine
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Hospices Civils de Lyon, Lyon, France.|NGS sequencing platform for molecular diagnosis, Hospices Civils de Lyon, Lyon, France.|Université de Lyon, Lyon, F-69003, France.|Université Lyon 1, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Millat
mesh_terms: D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization / Q000379:methods; D003241:Consanguinity; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006352:Heart Ventricles / Q000002:abnormalities; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D051191:Plakophilins / Q000235:genetics*; D035781:Siblings
chemical_list: C495337:PKP2 protein, human; D051191:Plakophilins
keywords: NGS sequencing; PKP2 deletion; arrhythmogenic right ventricular dysplasia/cardiomyopathy; cardiomyopathy; left ventricular non compaction