title: Tetralogy of Fallot and Hypoplastic Left Heart Syndrome - Complex Clinical Phenotypes Meet Complex Genetic Networks.
abstract: In many cases congenital heart disease (CHD) is represented by a complex phenotype and an array of several functional and morphological cardiac disorders. These malformations will be briefly summarized in the first part focusing on two severe CHD phenotypes, hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). In most cases of CHD the genetic origin remains largely unknown, though the complexity of the clinical picture strongly argues against a dysregulation which can be attributed to a single candidate gene but rather suggests a multifaceted polygenetic origin with elaborate interactions. Consistent with this idea, genome-wide approaches using whole exome sequencing, comparative sequence analysis of multiplex families to identify de novo mutations and global technologies to identify single nucleotide polymorphisms, copy number variants, dysregulation of the transcriptome and epigenetic variations have been conducted to obtain information about genetic alterations and potential predispositions possibly linked to the occurrence of a CHD phenotype. In the second part of this review we will summarize and discuss the available literature on identified genetic alterations linked to TOF and HLHS.
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany;
authors.forename: Harald
authors.initials: H
authors.lastname: Lahm
authors.affiliation: Department of Paediatric Cardiology and Congenital Heart Defects, German Heart Center Munich, Technische Universität München, D-80636 Munich, Germany;
authors.forename: Patric
authors.initials: P
authors.lastname: Schön
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany;
authors.forename: Stefanie
authors.initials: S
authors.lastname: Doppler
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany;
authors.forename: Martina
authors.initials: M
authors.lastname: Dreßen
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany;
authors.forename: Julie
authors.initials: J
authors.lastname: Cleuziou
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany;
authors.forename: Marcus-André
authors.initials: MA
authors.lastname: Deutsch
authors.affiliation: Department of Paediatric Cardiology and Congenital Heart Defects, German Heart Center Munich, Technische Universität München, D-80636 Munich, Germany; ; DZHK (German Center for Cardiovascular Research) - partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ewert
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany; ; DZHK (German Center for Cardiovascular Research) - partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lange
authors.affiliation: Department of Cardiovascular Surgery, Division of Experimental Surgery, German Heart Center Munich, Technische Universität München, Munich Heart Alliance, D-80636 Munich, Germany; ; DZHK (German Center for Cardiovascular Research) - partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krane
keywords: Congenital heart disease; Copy number variants; Epigenetics; Genome-wide association study; Hypoplastic left heart syndrome; Tetralogy of Fallot.; de novo mutations