European Journal of Pediatrics

, 169:207

DNA hypomethylation, transient neonatal diabetes, and prune belly sequence in one of two identical twins

  • Lene Bjerke Laborie
  • Deborah J. G. Mackay
  • I. Karen Temple
  • Anders Molven
  • Oddmund Søvik
  • Pål Rasmus Njølstad
Original Paper

DOI: 10.1007/s00431-009-1008-y

Cite this article as:
Laborie, L.B., Mackay, D.J.G., Temple, I.K. et al. Eur J Pediatr (2010) 169: 207. doi:10.1007/s00431-009-1008-y

Abstract

One known genetic mechanism for transient neonatal diabetes is loss of methylation at 6q24. The etiology of prune belly sequence is unknown but a genetic defect, affecting the mesoderm from which the triad abdominal muscle hypoplasia, urinary tract abnormalities, and cryptorchidism develop, has been suggested. We investigated a family, including one twin, with transient neonatal diabetes and prune belly sequence. Autoantibody tests excluded type 1 diabetes. Microsatellite marker analysis confirmed the twins being monozygotic. We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. The loss of methylation on chromosome 6q24 and elsewhere may indicate a generalized maternal hypomethylation syndrome, which accounts for both transient neonatal diabetes and prune belly sequence.

Keywords

Neonatal diabetesImprinting anomalyChromosome 6DNA methylationPrune belly syndrome

Abbreviations

BWS

Beckwith–Wiedemann syndrome

GAD

Glutamic acid decarboxylase

IA-2

Protein tyrosine phosphatase-like molecule

LOM

Loss of methylation

MEST

Mesoderm-specific transcript

MLPA

Multiplex ligation-dependent probe amplification

MSP

Methylation-specific PCR

NDM

Neonatal diabetes mellitus

OGTT

Oral glucose tolerance test

PBS

Prune belly sequence

pUPD

Paternal uniparental isodisomy

TNDM

Transient neonatal diabetes mellitus

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Lene Bjerke Laborie
    • 1
    • 2
  • Deborah J. G. Mackay
    • 3
    • 4
  • I. Karen Temple
    • 3
    • 5
  • Anders Molven
    • 6
    • 7
  • Oddmund Søvik
    • 2
  • Pål Rasmus Njølstad
    • 1
    • 2
  1. 1.Department of PediatricsHaukeland University HospitalBergenNorway
  2. 2.Department of Clinical MedicineUniversity of BergenBergenNorway
  3. 3.Division of Human GeneticsUniversity of SouthamptonSouthamptonUK
  4. 4.Wessex Regional Genetics LaboratorySalisbury District HospitalSalisburyUK
  5. 5.Wessex Clinical Genetic Service Southampton University Hospitals TrustSouthamptonUK
  6. 6.The Gade InstituteUniversity of BergenBergenNorway
  7. 7.Department of PathologyHaukeland University HospitalBergenNorway