Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome

Genet Med. 2017 Apr;19(4):476-482. doi: 10.1038/gim.2016.123. Epub 2016 Sep 15.


Purpose: 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).

Methods: 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.

Results: 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.

Conclusion: This study indicates the presence of MLIDs in TS14 patients but not in KOS14 patients.Genet Med 19 4, 476-482.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 14 / genetics*
  • CpG Islands
  • DNA Methylation*
  • DNA-Binding Proteins / genetics
  • Genetic Testing / methods*
  • Genomic Imprinting
  • Humans
  • Mutation
  • Transcription Factors / genetics
  • Uniparental Disomy / genetics*


  • DNA-Binding Proteins
  • Transcription Factors
  • ZDBF2 protein, human
  • ZNF597 protein, human

Supplementary concepts

  • Uniparental disomy, paternal, chromosome 14