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An Italian MODY family with proband and son carrying variants in GCK and HFN1A: is it a true case of digenic MODY?

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Abstract

Maturity Onset Diabetes of the Young (MODY) is a monogenic autosomal dominant disorder affecting 1-5 % of all patients with diabetes mellitus. In Caucasians, GCK and HNF1A mutations are the most common cause of MODY. Here, we report two family members carrying a genetic variant of both GCK and HNF1A gene and their nine year clinical follow-up. Our report urges physicians to be cautious when variants in two genes are found in a single patient and suggests that collaboration with MODY genetics experts is necessary for correct diagnosis and treatment.

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Abbreviations

BMI:

Body mass index

FBG:

Fasting blood glucose

FCP:

Fasting C-peptide

GAD-Ab:

Glutamic acid decarboxylase antibody

GCK :

Glucokinase

HbA1c:

Glycated hemoglobin

HDL-C:

High-density lipoprotein cholesterol

HNF1 A :

HNF1 homeobox A

HNF4 A :

Hepatocyte nuclear factor-4 alpha

IA2-Ab:

Insulinoma-associated protein-2 antibody

PDX1 :

Pancreatic and duodenal homeobox 1

LDL-C:

Low-density lipoprotein cholesterol

MODY:

Maturity-onset diabetes of the young

NeuroD1 :

Neurogenic differentiation 1

TG:

Triglycerides

References

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Acknowledgements

We thank the Director of the Diabetes Unit of University Hospital of Pisa, Prof. Piero Marchetti, for his support.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Section of Diabetes and Metabolic Diseases, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Daniela Lucchesi

  2. Unit of Pediatric Endocrinolgy and Diabetes, Maternal and Child Department, Azienda Ospedaliero-Univeristaria Pisana, Pisa, Italy

    Emioli Randazzo

  3. Sant’Anna School of Advanced Studies, Pisa, Italy

    Stefano Del Prato

  4. Section of Diabetes and Metabolic Diseases, Department of Medical Specialties, Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, Pisa, Italy

    Cristina Bianchi

Authors
  1. Daniela Lucchesi
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  2. Emioli Randazzo
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  3. Stefano Del Prato
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  4. Cristina Bianchi
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Corresponding author

Correspondence to Cristina Bianchi.

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Conflict of interest

Daniela Lucchesi and Emioli Randazzo report no duality of interest. Stefano Del Prato declares grants from AstraZeneca and Boehringer Ingelheim, consulting fees from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharpe and Dohme, Novartis Pharmaceuticals, Novo Nordisk and Sanofi, and honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharpe and Dohme, Novartis Pharmaceuticals, Novo Nordisk and Sanofi. Cristina Bianchi reports consulting fees and grants from Lilly, Novo Nordisk, MSD.

Ethical standard

The proband, who has given consent to the anonymous publication of the clinical report, was born in 1972 from eutocic childbirth, with a birth weight of 2750 g. Family history was positive for diabetes mellitus (father and paternal grandfather); none of them experienced chronic diabetes complications.

Informed consent

The article describes a clinical report anonymously, in agreement with the patient who provided informed consent.

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Managed by Fabrizio Barbetti.

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Lucchesi, D., Randazzo, E., Del Prato, S. et al. An Italian MODY family with proband and son carrying variants in GCK and HFN1A: is it a true case of digenic MODY?. Acta Diabetol 61, 131–134 (2024). https://doi.org/10.1007/s00592-023-02171-3

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  • DOI: https://doi.org/10.1007/s00592-023-02171-3

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