title: Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome.
abstract: Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth, midline abdominal wall defects, macroglossia, and embryonal tumors, is a model for understanding the relationship between genomic imprinting, human development, and cancer. The causes are heterogeneous, involving multiple genes on 11p15 and including infrequent mutation of p57(KIP2) or loss of imprinting of either of two imprinted gene domains on 11p15: LIT1, which is near p57(KIP2), or H19/IGF2. Unlike Prader-Willi and Angelman syndromes, no chromosomal deletions have yet been identified. Here we report a microdeletion including the entire LIT1 gene, providing genetic confirmation of the importance of this gene region in BWS. When inherited maternally, the deletion causes BWS with silencing of p57(KIP2), indicating deletion of an element important for the regulation of p57(KIP2) expression. When inherited paternally, there is no phenotype, suggesting that the LIT1 RNA itself is not necessary for normal development in humans.
authors.affiliation: Predoctoral Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Niemitz
authors.forename: Michael R
authors.initials: MR
authors.lastname: DeBaun
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fallon
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kugoh
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; D017353:Gene Deletion; D015870:Gene Expression; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008565:Membrane Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; C485621:KCNQ1OT1 long non-coding RNA, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D024642:Potassium Channels, Voltage-Gated