Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster

Hum Mutat. 2008 Sep;29(9):1141-6. doi: 10.1002/humu.20771.

Abstract

Maternal uniparental disomy 14 [upd(14)mat] is associated with a recognizable phenotype that includes pre- and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. Chromosome 14 contains an imprinted gene cluster, which is regulated by a differentially methylated region (IG-DMR) between DLK1 and GTL2. Here we report on four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. In three of the patients loss of paternal methylation appears to be a primary epimutation, whereas the other patient has a paternally derived deletion of -1 Mb that includes the imprinted DLK1-GTL2 gene cluster. These findings demonstrate that the upd(14)mat phenotype is caused by altered expression of genes within this cluster.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Calcium-Binding Proteins
  • Child
  • Chromosomes, Human, Pair 14 / genetics*
  • DNA Methylation
  • DNA Mutational Analysis
  • Epigenesis, Genetic*
  • Female
  • Gene Deletion
  • Genomic Imprinting
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mothers
  • Multigene Family
  • Mutation*
  • Proteins
  • RNA, Long Noncoding
  • Uniparental Disomy / genetics*
  • Uniparental Disomy / physiopathology

Substances

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