title: Novel microdeletions on chromosome 14q32.2 suggest a potential role for non-coding RNAs in Kagami-Ogata syndrome.
abstract: In approximately 20% of individuals with Kagami-Ogata syndrome (KOS14, MIM 608149), characterized by a bell-shaped thorax with coat-hanger configuration of the ribs, joint contractures, abdominal wall defects and polyhydramnios during the pregnancy, the syndrome is caused by a maternal deletion of the imprinted gene cluster in chromosome 14q32.2. Most deletions reported so far included one or both of the differentially methylated regions (DMRs) - DLK1/MEG3 IG-DMR and MEG3-DMR. We present two unrelated families with two affected siblings each, presenting with classical KOS14 due to maternally inherited microdeletions. Interestingly, all four patients have lived through to adulthood, even though mortality rates for patients with KOS14 due to a microdeletion are relatively high. In the first family, none of the DMRs is included in the deletion and the methylation status is identical to that of controls. Deletions that do not encompass the DMRs in this region are thus sufficient to elicit the full KOS14 phenotype. In the second family, a partially overlapping deletion including both DMRs and MEG3 was detected. In summary, we show that patients with KOS14 can live into adulthood, that causal deletions do not have to include the DMRs and that consequently a normal methylation pattern does not exclude KOS14.
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Ilse M
authors.initials: IM
authors.lastname: van der Werf
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Czeschik
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: Reyniers
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Vandeweyer
authors.affiliation: Department of Neonatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Vanhaesebrouck
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Lüdecke
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.|Institut für Humangenetik, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Jules G
authors.initials: JG
authors.lastname: Leroy
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: R Frank
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D006801:Humans; D010375:Pedigree; D010641:Phenotype; D022661:RNA, Untranslated / Q000235:genetics*; D017384:Sequence Deletion; D013577:Syndrome; D024182:Uniparental Disomy / Q000175:diagnosis / Q000235:genetics*; D000096803:Imprinting Disorders
chemical_list: D022661:RNA, Untranslated