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.
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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
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Acknowledgments
We thank the University of Bergen, Haukeland University Hospital, Innovest, Translational Medicine Fund, the Research Council of Norway, and Diabetes UK for financial support.
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The authors declare that they have no conflict of interest.
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Laborie, L.B., Mackay, D.J.G., Temple, I.K. et al. DNA hypomethylation, transient neonatal diabetes, and prune belly sequence in one of two identical twins. Eur J Pediatr 169, 207–213 (2010). https://doi.org/10.1007/s00431-009-1008-y
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DOI: https://doi.org/10.1007/s00431-009-1008-y