Acta Diabetologica

, Volume 56, Issue 3, pp 301–307 | Cite as

Transient neonatal diabetes mellitus and hypomethylation at additional imprinted loci: novel ZFP57 mutation and review on the literature

  • Ameni Touati
  • Javier Errea-Dorronsoro
  • Sonia Nouri
  • Yosra Halleb
  • Arrate Pereda
  • Nabiha Mahdhaoui
  • Aida Ghith
  • Ali Saad
  • Guiomar Perez de Nanclares
  • Dorra H’mida ben brahimEmail author
Original Article



6q24-related transient neonatal diabetes mellitus (6q24-TNDM) is a rare imprinting disorder characterized by uncontrolled hyperglycemia during the first 6 months of life. The molecular etiology of 6q24-TNDM is attributable to overexpression of the paternally inherited PLAGL1 and HYMAI genes located on the 6q24 locus. One of these major defects is maternal loss of methylation (LOM) at 6q24. In addition, approximately 50% of TNDM patients that present LOM at 6q24 can also display hypomethylation at additional imprinted loci (multilocus imprinting disturbances, MLID). Interestingly, the majority of these patients carry mutations in the ZFP57 gene, a transcription factor required for the adequate maintenance of methylation during early embryonic development.


Methylation analysis of 6q24 and additional imprinted loci was carried out by MS-MLPA in a Tunisian male patient with clinical diagnosis of TNMD. For the same patient, mutation analysis of the ZFP57 gene was conducted by direct Sanger sequencing.


We report a novel nonsense mutation (c.373C > T; p.R125*; ENST00000376883.1) at the ZFP57 gene causing TNDM-MLID and describe detailed phenotype/epigenotype analysis of TNMD patients carrying ZFP57 mutations.


We provide additional support to the role of ZFP57 as a genetic determinant cause of MLID in patients with TNMD.


Transient neonatal diabetes mellitus Multilocus imprinting disturbances (MLID) ZFP57 gene Tunisia 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Ethical approval

Ethical procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national, local ethics committee: Comitato Etico Centrale IRCCS Lazion, Sezione IFO/Fondazione Bietti, Rome, Italy) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from the patient included in the study.

Supplementary material

592_2018_1239_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 11 KB)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Ameni Touati
    • 1
    • 2
  • Javier Errea-Dorronsoro
    • 3
  • Sonia Nouri
    • 4
    • 5
  • Yosra Halleb
    • 1
    • 5
  • Arrate Pereda
    • 3
  • Nabiha Mahdhaoui
    • 4
    • 5
  • Aida Ghith
    • 4
    • 5
  • Ali Saad
    • 1
    • 5
  • Guiomar Perez de Nanclares
    • 3
  • Dorra H’mida ben brahim
    • 1
    • 5
    Email author
  1. 1.Department of Human Cytogenetics, Molecular Genetics and Reproductive BiologyFarhat HACHED University HospitalSousseTunisia
  2. 2.High Institute of BiotechnologyMonastir UniversityMonastirTunisia
  3. 3.Molecular (Epi)Genetic Lab, BioAraba National Health InstituteOSI Araba University HospitalVitoria-GasteizSpain
  4. 4.Department of NeonatologyFarhat HACHED University HospitalSousseTunisia
  5. 5.Faculty of MedicineSousse UniversitySousseTunisia

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