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Epimutation of the TNDM locus and the Beckwith–Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus

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Abstract

Transient neonatal diabetes mellitus (TNDM) is characterised by intra-uterine growth retardation, while Beckwith–Wiedemann syndrome (BWS) is a clinically heterogeneous overgrowth syndrome. Both TNDM and BWS may be caused by aberrant loss of methylation (LOM) at imprinted loci on chromosomes 6q24 and 11p15.5 respectively. Here we describe two patients with a clinical diagnosis of TNDM caused by LOM at the maternally methylated imprinted domain on 6q24; in addition, these patients had LOM at the centromeric differentially methylated region of 11p15.5. This shows that imprinting anomalies can affect more than one imprinted locus and may alter the clinical presentation of imprinted disease.

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Abbreviations

BWS:

Beckwith–Wiedemann syndrome

DMR:

Differentially methylated region

IUGR:

Intra-uterine growth retardation

LOM:

Loss of methylation

MS-PCR:

Methylation-specific PCR

MLPA:

Multiplex ligation-dependent probe amplification

TNDM:

Transient neonatal diabetes mellitus

UPD:

Uniparental disomy

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Acknowledgements

This work was funded by Diabetes UK. The authors gratefully acknowledge the many clinicians who provided DNA samples and clinical information for the individuals involved in this study.

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Authors and Affiliations

  1. Wessex Regional Genetics Laboratory, Salisbury District Hospital, SP2 8BJ, Salisbury, UK

    D. J. G Mackay, D. J. Bunyan, N. S. Thomas & D. O. Robinson

  2. Human Genetics Division, University of Southampton, Southampton, UK

    D. J. G Mackay, N. S. Thomas, D. O. Robinson & I. K. Temple

  3. Medical Genetics Laboratory Centre, The Kennedy Institute – National Eye Clinic, Glostrup, Denmark

    J. M. D. Hahnemann

  4. Clinical Genetics, The Kennedy Institute - National Eye Clinic, Glostrup, Denmark

    S. E. Boonen

  5. Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark

    S. Poerksen

  6. National Genetics Reference Laboratory Wessex, Salisbury, UK

    H. E. White & V. J. Durston

  7. Bristol Royal Hospital for Children, University of Bristol, Bristol, UK

    J. P. H Shield

  8. Academic Department of Medical Genetics, St Mary’s Hospital, Manchester, UK

    J. Clayton-Smith

  9. Wessex Clinical Genetics Service, The Princess Anne Hospital, Southampton, UK

    I. K. Temple

Authors
  1. D. J. G Mackay
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  2. J. M. D. Hahnemann
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  3. S. E. Boonen
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  4. S. Poerksen
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  5. D. J. Bunyan
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  6. H. E. White
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  7. V. J. Durston
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  8. N. S. Thomas
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  9. D. O. Robinson
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  10. J. P. H Shield
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  11. J. Clayton-Smith
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  12. I. K. Temple
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Corresponding author

Correspondence to D. J. G Mackay.

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Mackay, D.J.G., Hahnemann, J.M.D., Boonen, S.E. et al. Epimutation of the TNDM locus and the Beckwith–Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus. Hum Genet 119, 179–184 (2006). https://doi.org/10.1007/s00439-005-0127-4

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  • DOI: https://doi.org/10.1007/s00439-005-0127-4

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