Article Text

Download PDFPDF
Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13 patients with transient neonatal diabetes: new hypothesis raised by the finding of a unique case with hemizygotic deletion in the critical region
  1. C Diatloff-Zito1,*,
  2. A Nicole1,
  3. G Marcelin1,
  4. H Labit1,
  5. E Marquis1,
  6. C Bellanné-Chantelot2,
  7. J J Robert3
  1. 1Inserm U781, Université Paris 5, Paris, France
  2. 2Département de Cytogénétique, Université Pierre et Marie Curie, AP-HP Saint Antoine, Paris, France
  3. 3Faculté de Médecine Paris 5, Fédération de Pédiatrie, Hôpital Necker-Enfants Malades, Paris, France
  1. Correspondence to:
 Dr C Diatloff-Zito
 Inserm U781 Groupe Hospitalier Necker Enfants-Malades, 149-161 rue de Sèvres 75743, Paris Cedex 15, France;diatloff{at}


Background: Transient neonatal diabetes (TND) is a rare form of diabetes usually present in the first few days after birth that resolves within 1 year but that has a tendency to recur later in life. It can be associated with chromosome 6 paternal uniparental disomy (UPD), paternal duplications or loss of maternal methylation at the 6q24 imprinted locus.

Objective: To report on a cohort of 13 sporadic TND cases, including five with birth defects (congenital abnormalities of heart, brain and bone) and eight without.

Results: The hallmarks of diabetes were similar in patients with or without 6q24 defects. The chromosome 6 abnormalities in our patients (n = 13) included 2 of 13 (approximately 15.4%) cases of paternal UPD6, 2 of 11 (approximately 18%) cases of complete and 3 of 11 (approximately 27%) cases of partial loss of the maternal methylation signature upstream of ZAC1-HYMAI imprinted genes in non-UPD cases, and 1 of 13 (approximately 7.7%) cases of hemizygotic deletion.

Conclusion: The deletion was found in a patient with severe congenital abnormalities. This genetic lesion was not reported previously. The hypothesis of an effect on regulatory elements critical for imprinting and tissue-specific gene expression in early development by the deletion is raised. The data presented here may contribute to the diagnosis and the understanding of imprinting in the region.

  • CGi, CpG islands
  • DMR, differentially methylated region
  • ICE, imprinting control element
  • PCR, polymerase chain reaction
  • TND, transient neonatal diabetes
  • UPD, uniparental disomy
  • transient neonatal diabetes
  • genetics
  • imprinting
  • methylation
  • deletion

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • * CNRS. GM holds a PhD fellowship from the Ministère de l’Education Nationale de la Recherche et de la Technologie and Université Pierre et Marie Curie, Paris 6.

  • Published Online First 13 September 2006

  • Funding: This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (Inserm) and the Association Aide aux Jeunes Diabètiques (AJD).

  • Competing interests: None.