title: Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome.
abstract: Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14).
  
  
  
  We studied four TS14 patients (patients 1-4) and five KOS14 patients (patients 5-9) with epimutations. We performed HumanMethylation450 BeadChip (HM450k) analysis for 43 differentially methylated regions (DMRs) (753 CpG sites) and pyrosequencing for 12 DMRs (62 CpG sites) using leukocyte genomic DNA (Leu-gDNA) of patients 1-9, and performed HM450k analysis for 43 DMRs (a slightly different set of 753 CpG sites) using buccal cell gDNA (Buc-gDNA) of patients 1, 3, and 4. We also performed mutation analysis for six causative and candidate genes for MLIDs and quantitative expression analysis using immortalized lymphocytes in MLID-positive patients.
  
  
  
  Methylation analysis showed hypermethylated ZDBF2-DMR and ZNF597/NAA60-DMR, hypomethylated ZNF597-DMR in both Leu-gDNA and Buc-gDNA, and hypomethylated PPIEL-DMR in Buc-gDNA of patient 1, and hypermethylated GNAS-A/B-DMR in Leu-gDNA of patient 3. No mutations were detected in the six genes for MLIDs. Expression patterns of ZDBF2, ZNF597, and GNAS-A/B were consistent with the identified MLIDs.
  
  
  
  This study indicates the presence of MLIDs in TS14 patients but not in KOS14 patients.Genet Med 19 4, 476-482.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kagami
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Akie
authors.identifier: 0000-0001-6632-7426
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sano
authors.affiliation: Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kohji
authors.identifier: 0000-0001-9747-5069
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenichiro
authors.identifier: 0000-0002-7809-7637
authors.initials: K
authors.lastname: Hata
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tsutomu
authors.identifier: 0000-0001-7178-9991
authors.initials: T
authors.lastname: Ogata
mesh_terms: D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D018392:Genomic Imprinting; D006801:Humans; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics*; D000096803:Imprinting Disorders
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C000624166:ZDBF2 protein, human; C000619298:ZNF597 protein, human