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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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