Deborah Mackay, Ph.D. is a senior lecturer in human genetics at the University of Southampton, UK, and heads the Wessex Imprinting Group, which is embedded in a service genetics laboratory and delivers wide-ranging translational research into human imprinting disorders.
Transient neonatal diabetes mellitus type 1†
Version of Record online: 20 AUG 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Imprinted Genes and Human Disease
Volume 154C, Issue 3, pages 335–342, 15 August 2010
How to Cite
Mackay, D. J.G. and Temple, I. K. (2010), Transient neonatal diabetes mellitus type 1. Am. J. Med. Genet., 154C: 335–342. doi: 10.1002/ajmg.c.30272
How to cite this article: Mackay DJG, Temple IK. 2010. Transient neonatal diabetes mellitus type 1. Am J Med Genet Part C Semin Med Genet 153C:335–342.
- Issue online: 20 AUG 2010
- Version of Record online: 20 AUG 2010
- DNA methylation;
- transient neonatal diabetes
Transient neonatal diabetes mellitus type 1 (TNDM1) is a rare but remarkable form of diabetes which presents in infancy, resolves in the first months of life, but then frequently recurs in later life. It is caused by overexpression of the imprinted genes PLAGL1 and HYMAI on human chromosome 6q24. The expression of these genes is normally restricted to the paternal allele as a result of maternal DNA methylation. TNDM1 is not associated with mutation of PLAGL1 or HYMAI, but rather with their overexpression via uniparental disomy, chromosome duplication, or relaxation of imprinting. Study of patients with TNDM1 has provided valuable insights into the causes of imprinting disorders. Over half of patients with maternal hypomethylation at the TNDM1 locus have additional hypomethylation of other maternally methylated imprinted genes throughout the genome, and the majority of these patients have mutations in the transcription factor ZFP57. TNDM1 with maternal hypomethylation has also been observed in patients conceived by assisted reproduction, and in discordant monozygotic twins. The variable clinical features of TNDM1 may be associated with variation in the nature of the underlying epigenetic and genetic mutations, and future study of this disorder is likely to yield further insights not only into the biological mechanisms of imprinting, but also into the contribution of epigenetics to diabetes. © 2010 Wiley-Liss, Inc.