Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus

Hum Genet. 2002 Feb;110(2):139-44. doi: 10.1007/s00439-001-0671-5. Epub 2002 Jan 24.

Abstract

Transient neonatal diabetes mellitus (TNDM) is a rare disease believed to result from overexpression of a paternally expressed gene controlled by a differentially methylated CpG island on chromosome 6q24. Two genes partially overlap the island: the cell-cycle-control gene ZAC and the untranslated gene HYMAI, the function of which is currently unknown. Proof that either gene is involved in TNDM would require demonstration that imprinted expression is relaxed in TNDM patients; this has hitherto been lacking because of the rarity of the disease and the lack of imprinted expression in the lymphoblastoid cells that are generally the only resource available for study. Here, we show, for the first time, the aberrant expression of imprinted genes in a TNDM patient. In TNDM fibroblasts, the monoallelic expression of both ZAC and HYMAI is relaxed, providing strong supportive evidence that the presence of two unmethylated alleles of this locus is indeed associated with the inappropriate gene expression of neighbouring genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6*
  • DNA Primers
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Diabetes Mellitus / genetics*
  • Genes, Tumor Suppressor*
  • Genomic Imprinting*
  • Humans
  • Infant, Newborn
  • Male
  • Polymorphism, Single Nucleotide
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics*
  • Transcription Factors*
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA Primers
  • DNA, Complementary
  • PLAGL1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins