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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}necker.fr

Abstract

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

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Footnotes

  • * 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.

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