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Monogenic Diabetes

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Diabetes Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

Monogenic forms of diabetes can be associated with diabetes diagnosed in neonatal life or in young adulthood.

The commonest presentation of monogenic diabetes is maturity-onset diabetes of the young (MODY), which typically presents in young adult life with familial, non-autoimmune diabetes without insulin resistance. HNF1A and GCK mutations account for most cases.

Mitochondrial diabetes presents at a similar age with diabetes associated with deafness, myopathy, and neurological features.

In the first 6 months of life, diabetes is nearly always caused by single gene mutations. Neonatal diabetes is highly heterogeneous, but the commonest causes are mutations in KCNJ11 and ABCC8 encoding the beta-cell KATP channel components and methylation defects in the chromosome 6q24 region.

The most important reason for diagnosing monogenic diabetes is that the genetic aetiology alters treatment. Mutations in HNF1A, HNF4A, ABCC8, and KCNJ11 all lead to diabetes responsive to sulfonylurea therapy, while GCK-MODY does not require treatment.

When diabetes arises as part of a multisystem disorder such as in Wolcott-Rallison syndrome or HNF1B-MODY, the genetic diagnosis may give important insight into prognosis and development of other features.

New sequencing technologies such as exome sequencing can be used to search for new genes which cause diabetes, but interpreting novel genetic variants in both familiar and less well-known genes remains extremely challenging.

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Authors and Affiliations

  1. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

    Katharine R. Owen

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  1. Katharine R. Owen
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Correspondence to Katharine R. Owen .

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Editors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy

    Enzo Bonora

  2. Diabetes Division, Diabetes Research Unit, University of Texas Health Science Center, San Antonio, TX, USA

    Ralph A. DeFronzo

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Owen, K.R. (2018). Monogenic Diabetes. In: Bonora, E., DeFronzo, R. (eds) Diabetes Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment . Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-45015-5_10

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  • DOI: https://doi.org/10.1007/978-3-319-45015-5_10

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