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Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing

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Abstract

Aims

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern. The diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of next-generation sequencing in the Tunisian population.

Methods

We performed a targeted sequencing of 27 genes known to cause monogenic diabetes in 11 phenotypically suspected Tunisian patients. We retained genetic variants passing filters of frequency in public databases as well as their probable effects on protein structures and functions evaluated by bioinformatics prediction tools.

Results

Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice-site variants were identified in ABCC8 gene.

Conclusions

Our study is the first to investigate the clinical application of targeted next-generation sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population.

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Acknowledgements

We thank the patients, their parents and healthcare professionals who participated in this study. We also thank the CSS-Mendel Institute (Rome, Italy) for the collaboration and the provision of infrastructure for this research. This work was supported by Institut Pasteur of Tunis (PCI-15) and the Tunisian Ministry of higher Education and Scientific Research (LR11 IPT05). This study was partly supported by the Italian Ministry of Health (“Ricerca Corrente 2015–2017” to S. Prudente).

Author information

Authors and Affiliations

  1. Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002, Tunis, Tunisia

    Hamza Dallali, Meriem Hechmi, Sahar Elouej, Haifa Jmel, Yosra Ben Halima, Mariem Chargui, Mariem Gharbi, Henda Jamoussi, Abdelmajid Abid, Sonia Abdelhak & Rym Kefi

  2. National Institute of Applied Sciences and Technology, University of Carthage, Tunis, Tunisia

    Hamza Dallali & Meriem Hechmi

  3. Research Unit of Metabolic and Cardiovascular Diseases, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Serena Pezzilli, Luana Mercuri, Federica Alberico, Vincenzo Trischitta & Sabrina Prudente

  4. Department of Experimental Medicine, Sapienza University, Rome, Italy

    Serena Pezzilli & Vincenzo Trischitta

  5. Fattouma Bourguiba University Hospital, Monastir, Tunisia

    Om Kalthoum Sallem

  6. Faculty of Medicine La Timone, INSERM, GMGF, Aix Marseille University, 27 bd Jean Moulin, 13385, Marseille, France

    Sahar Elouej

  7. Faculty of Sciences of Bizerte, University of Carthage, Tunis, Tunisia

    Haifa Jmel

  8. University of Tunis El Manar, El Manar I, 2092, Tunis, Tunisia

    Yosra Ben Halima, Sonia Abdelhak & Rym Kefi

  9. Unit of Bioinformatics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Tommaso Mazza

  10. Central Laboratory of Medical Biology, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002, Tunis, Tunisia

    Afaf Bahlous

  11. Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002, Tunis, Tunisia

    Melika Ben Ahmed

  12. Research Unit on Obesity, National Institute of Nutrition and Food Technology, 11 rue Jebel Lakhdar, Bab Saadoun, 1007, Tunis, Tunisia

    Henda Jamoussi & Abdelmajid Abid

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  1. Hamza Dallali
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  2. Serena Pezzilli
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  3. Meriem Hechmi
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  5. Sahar Elouej
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  6. Haifa Jmel
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  7. Yosra Ben Halima
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  11. Federica Alberico
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  18. Sonia Abdelhak
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  19. Sabrina Prudente
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  20. Rym Kefi
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Corresponding author

Correspondence to Rym Kefi.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were approved by Institut Pasteur of Tunis ethics committee (Reference: 2016/19/I/LR11IPT05) and were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Dallali, H., Pezzilli, S., Hechmi, M. et al. Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing. Acta Diabetol 56, 515–523 (2019). https://doi.org/10.1007/s00592-018-01283-5

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