Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities

Am J Hum Genet. 2000 Dec;67(6):1586-91. doi: 10.1086/316897. Epub 2000 Oct 18.

Abstract

Neonatal diabetes, which can be transient or permanent, is defined as hyperglycemia that presents within the first month of life and requires insulin therapy. Transient neonatal diabetes mellitus has been associated with abnormalities of the paternally inherited copy of chromosome 6, including duplications of a portion of the long arm of chromosome 6 and uniparental disomy, implicating overexpression of an imprinted gene in this disorder. To date, all patients with transient neonatal diabetes mellitus and uniparental disomy have had complete paternal isodisomy. We describe a patient with neonatal diabetes, macroglossia, and craniofacial abnormalities, with partial paternal uniparental disomy of chromosome 6 involving the distal portion of 6q, from 6q24-qter. This observation demonstrates that mitotic recombination of chromosome 6 can also give rise to uniparental disomy and neonatal diabetes, a situation similar to that observed in Beckwith-Wiedemann syndrome, another imprinted disorder. This finding has clinical implications, since somatic mosaicism for uniparental disomy of chromosome 6 should also be considered in patients with transient neonatal diabetes mellitus.

MeSH terms

  • Aneuploidy*
  • Chromosomes, Human, Pair 6 / genetics*
  • Craniofacial Abnormalities / complications
  • Craniofacial Abnormalities / genetics*
  • Diabetes Complications
  • Diabetes Mellitus / congenital*
  • Diabetes Mellitus / genetics
  • Fathers
  • Female
  • Genomic Imprinting / genetics*
  • Humans
  • Infant, Newborn
  • Macroglossia / complications
  • Macroglossia / congenital
  • Macroglossia / genetics*
  • Male
  • Microsatellite Repeats / genetics
  • Mosaicism / genetics
  • Recombination, Genetic / genetics