title: Next-generation sequencing (NGS) as a fast molecular diagnosis tool for left ventricular noncompaction in an infant with compound mutations in the MYBPC3 gene.
abstract: Left ventricular noncompaction (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. LVNC is classified as a rare genetic cardiomyopathy. Molecular diagnosis is a challenge for the medical community as the condition shares morphologic features of hypertrophic and dilated cardiomyopathies. 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. In this report, we describe a case of a severe form of LVNC leading to death at 6 months of life. NGS sequencing using a custom design for hypertrophic cardiomyopathy panel allowed us to identify compound heterozygosity in the MYBPC3 gene (p.Lys505del, p.Pro955fs) in 3 days, confirming NGS sequencing as a fast molecular diagnosis tool. Other studies have reported neonatal presentation of cardiomyopathies associated with compound heterozygous or homozygous MYBPC3 mutations. In this family and in families in which parental truncating MYBPC3 mutations are identified, preimplantation or prenatal genetic screening should be considered as these genotypes leads to neonatal mortality and morbidity.
authors.affiliation: Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Schaefer
authors.affiliation: Unité médico-chirurgicale de cardiopédiatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Helms
authors.affiliation: Service de Pathologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Marcellin
authors.affiliation: Service de Réanimation Pédiatrique Spécialisée-Surveillance Continue, Pédiatrie 2, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprez
authors.affiliation: Service de Chirurgie Cardiaque, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Billaud
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Chanavat
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Rousson
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, France. Electronic address: gilles.millat@chu-lyon.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Millat
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007223:Infant; D056830:Isolated Noncompaction of the Ventricular Myocardium / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009154:Mutation; D010375:Pedigree; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C
keywords: Cardiomyopathy; Left ventricular noncompaction; MYBPC3; Molecular diagnosis; NGS