Epimutation (hypomethylation) affecting the chromosome 14q32.2 imprinted region in a girl with upd(14)mat-like phenotype

Eur J Hum Genet. 2008 Aug;16(8):1019-23. doi: 10.1038/ejhg.2008.90. Epub 2008 May 14.

Abstract

Maternal uniparental disomy for chromosome 14 (upd(14)mat) causes clinically discernible features such as pre- and/or postnatal growth failure, hypotonia, obesity, small hands, and early onset of puberty. The monoallelic expression patterns at the 14q32.2 imprinted region are tightly related to methylation status of the DLK1-MEG3 intergenic differential methylation region (DMR) and the MEG3-DMR that are severely hypermethylated after paternal transmission and grossly hypomethylated after maternal transmission. We examined this imprinted region in a 2 2/12-year-old Japanese patient who was born with a normal birth size (length, +0.2 SD; weight, -0.5 SD) and showed postnatal growth failure (height, -3.1 SD; weight, -3.4 SD), hypotonia, frontal bossing, micrognathia, and small hands. Methylation analysis, genotyping analysis, and deletion analysis were performed with blood samples of the patient and the parents, showing that the DMRs of this patient were grossly hypomethylated in the absence of upd(14)mat and deletion of the DMRs. The results indicate the occurrence of an epimutation (hypomethylation) affecting the normally methylated DMRs of paternal origin, and imply that epimutations should be examined in patients with upd(14)mat-like phenotype.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / etiology
  • Calcium-Binding Proteins
  • Child, Preschool
  • Chromosomes, Human, Pair 14 / genetics*
  • DNA Methylation*
  • DNA, Intergenic / genetics*
  • Fathers
  • Female
  • Genomic Imprinting*
  • Growth Disorders / etiology*
  • Growth Disorders / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Membrane Proteins / genetics
  • Mothers
  • Phenotype
  • Proteins / genetics
  • RNA, Long Noncoding
  • Uniparental Disomy / genetics*

Substances

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