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


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.


Neonatal diabetes Imprinting anomaly Chromosome 6 DNA methylation Prune belly syndrome 



Beckwith–Wiedemann syndrome


Glutamic acid decarboxylase


Protein tyrosine phosphatase-like molecule


Loss of methylation


Mesoderm-specific transcript


Multiplex ligation-dependent probe amplification


Methylation-specific PCR


Neonatal diabetes mellitus


Oral glucose tolerance test


Prune belly sequence


Paternal uniparental isodisomy


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

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