title: Congenital imprinting disorders: Application of multilocus and high throughput methods to decipher new pathomechanisms and improve their management.
abstract: Imprinting disorders (IDs) are a group of congenital diseases affecting growth, development and metabolism. They are caused by changes in the allele-specific regulation ("epigenetic mutation") or in the genomic sequence ("genetic mutation") of imprinted genes. Currently molecular tests in ID patients are generally restricted to single loci classically associated with the disease, but this approach limits diagnostic yield, because of the molecular and clinical heterogeneity between IDs. From the technical point of view, these limitations are aggravated by the lack of standardization in testing methodology, in the DNA sequences tested, and in clinical inclusion criteria prompting testing. However, an increasing number of new studies show that these problems can be addressed by the use of new tests targeting multiple loci and/or a total exome and genome analysis. The rapid development of efficient and high-throughput molecular techniques and their applications in research and diagnostics in the last decade have led to an impressive increase of knowledge on IDs and their basic pathomechanisms. In combination with the improvement of data recording and documentation, the diagnostic strategies are increasingly based on standardized protocols, and thereby provide the backbone for directed counseling, more personalized management, and new therapeutic approaches.
authors.affiliation: Institute of Human Genetics, University Hospital, RWTH Technical University Aachen, Aachen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Soellner
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), ĹHospitalet de Llobregat, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.affiliation: Faculty of Medicine, University of Southampton, UK; Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, UK.
authors.forename: Faisal I
authors.initials: FI
authors.lastname: Rezwan
authors.affiliation: Institute of Human Genetics, University Hospital, RWTH Technical University Aachen, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Begemann
authors.affiliation: Faculty of Medicine, University of Southampton, UK; Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Mackay
authors.affiliation: Institute of Human Genetics, University Hospital, RWTH Technical University Aachen, Aachen, Germany. Electronic address: teggermann@ukaachen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
mesh_terms: D000013:Congenital Abnormalities / Q000235:genetics*; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018392:Genomic Imprinting; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D058885:Multilocus Sequence Typing / Q000379:methods*; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: High throughput techniques; Imprinting disorders; Methylation-specific assay; Multilocus imprinting analysis