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

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.

Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

1. Department of Pediatrics, Haukeland University Hospital, 5021, Bergen, Norway
   Lene Bjerke Laborie & Pål Rasmus Njølstad
2. Department of Clinical Medicine, University of Bergen, Bergen, Norway
   Lene Bjerke Laborie, Oddmund Søvik & Pål Rasmus Njølstad
3. Division of Human Genetics, University of Southampton, Southampton, UK
   Deborah J. G. Mackay & I. Karen Temple
4. Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK
   Deborah J. G. Mackay
5. Wessex Clinical Genetic Service Southampton University Hospitals Trust, Southampton, UK
   I. Karen Temple
6. The Gade Institute, University of Bergen, Bergen, Norway
   Anders Molven
7. Department of Pathology, Haukeland University Hospital, Bergen, Norway
   Anders Molven

Authors

1. Lene Bjerke Laborie
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2. Deborah J. G. Mackay
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3. I. Karen Temple
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4. Anders Molven
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5. Oddmund Søvik
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6. Pål Rasmus Njølstad
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Correspondence toPål Rasmus Njølstad.

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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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• Received: 11 February 2009
• Accepted: 30 May 2009
• Published: 13 June 2009
• Issue Date: February 2010
• DOI: https://doi.org/10.1007/s00431-009-1008-y

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