Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

Nat Genet. 2008 Feb;40(2):237-42. doi: 10.1038/ng.2007.56. Epub 2008 Jan 6.


Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins
  • Case-Control Studies
  • Chromosome Breakage
  • Chromosomes, Human, Pair 14*
  • Computer Simulation
  • DNA Methylation
  • DNA, Intergenic
  • Fathers
  • Female
  • Gene Deletion*
  • Genomic Imprinting*
  • Heterozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intercellular Signaling Peptides and Proteins / genetics
  • Male
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Mothers
  • Mutation*
  • Pedigree
  • Phenotype
  • Physical Chromosome Mapping
  • Polymorphism, Single Nucleotide
  • Proteins / genetics
  • RNA, Long Noncoding
  • Regulatory Sequences, Nucleic Acid
  • Uniparental Disomy / genetics*


  • Calcium-Binding Proteins
  • DLK1 protein, human
  • DNA, Intergenic
  • Intercellular Signaling Peptides and Proteins
  • MEG3 non-coding RNA, human
  • Membrane Proteins
  • Proteins
  • RNA, Long Noncoding

Associated data

  • GENBANK/AL117190
  • GENBANK/CA396130
  • RefSeq/NC_000014
  • RefSeq/NM_001362
  • RefSeq/NM_003836
  • RefSeq/NR_002766
  • RefSeq/XM_370776