Monogenic Forms of Diabetes Mellitus

Gaál, Zsolt; Balogh, I

doi:10.1007/978-3-030-25905-1_18

Cited by 15 publications

(20 citation statements)

References 220 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, individuals with mutations in the glucokinase gene (MODY2) may remain asymptomatic until the development of insulin resistance during pregnancy and thus misdiagnosed as GDM [32]. Currently 15 different MODY genes have been identified (HNF4A; GCK; HNF1A; PDX1; HNF1B; NEUROD1; KLF11; CEL; PAX4; INS; BLK; ABCC8; KCNJ11; APPL1; RFX6), presenting age-dependent penetrance pending location of mutations [33]. A proper diagnosis of these types of monogenic diabetes is critical for accurate etiology-based treatment, which may lead to better glucose control and reducing both pregnancy complications as well as the effects in the offspring later in life.…”

Section: Etiology Of Gdm and Genetic Component Of The Diseasementioning

confidence: 99%

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Lorenzo

Martín-Montalvo

Vuilleumier

et al. 2019

IJMS

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM), a metabolic disease that develops with the increase in insulin resistance during late pregnancy, is currently one of the most common complications affecting pregnancy. The polygenic nature of GDM, together with the interplay between different genetic variants with nutritional and environmental factors has hindered the full understanding of the etiology of this disease. However, an important genetic overlap has been found with type 2 diabetes mellitus (T2DM) and, as in the case of T2DM, most of the identified loci are associated with β-cell function. Early detection of GDM and adequate interventions to control the maternal glycemia are necessary to avoid the adverse outcomes for both the mother and the offspring. The in utero exposure to the diabetic milieu predispose these children for future diseases, among them T2DM, originating a vicious circle implicated in the increased prevalence of both GDM and T2DM. The involvement of inflammatory processes in the development of GDM highlights the importance of pancreatic β-cell factors able to favor the adaptation processes required during gestation, concomitantly with the protection of the islets from an inflammatory milieu. In this regard, two members of the Pax family of transcription factors, PAX4 and PAX8, together with the chromatin remodeler factor HMG20A, have gained great relevance due to their involvement in β-cell mass adaptation together with their anti-inflammatory properties. Mutations in these factors have been associated with GDM, highlighting these as novel candidates for genetic screening analysis in the identification of women at risk of developing GDM.

show abstract

Section: Etiology Of Gdm and Genetic Component Of The Diseasementioning

confidence: 99%

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Lorenzo

Martín-Montalvo

Vuilleumier

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…The typical classification of monogenic diabetes includes two main subgroups; neonatal diabetes, usually presenting before 6 months of age, and maturity onset diabetes of the young (MODY), usually presenting in youth and adults. While neonatal diabetic cases are rare (1 in 1,000,000 birth), MODY disorders are more common, accounting for 1–5% of all diabetic cases ( 1 – 4 ). The acronym MODY was first used in 1975 by Fajans and Tattersall, to distinguish a hereditary form of diabetes presented in juvenile patients from classical type 1 diabetes patients ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Modeling Maturity Onset Diabetes of the Young in Pluripotent Stem Cells: Challenges and Achievements

Braverman-Gross

Benvenisty

2021

Front. Endocrinol.

View full text Add to dashboard Cite

Maturity onset diabetes of the young (MODY), is a group of monogenic diabetes disorders. Rodent models for MODY do not fully recapitulate the human phenotypes, calling for models generated in human cells. Human pluripotent stem cells (hPSCs), capable of differentiation towards pancreatic cells, possess a great opportunity to model MODY disorders in vitro. Here, we review the models for MODY diseases in hPSCs to date and the molecular lessons learnt from them. We also discuss the limitations and challenges that these types of models are still facing.

show abstract

“…This usually precedes the beta-cell insulin secretion defect for years and it is not characteristic of HNF4A -MODY [ 17 ]. HNF1A -MODY has age-dependent high penetrance; almost 63% of the patients with HNF1A mutations develop symptoms by the age of 25, 93.6% by the age of 50 years, and 98.7% by the age of 75 years [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…As a result, HNF1B -MODY patients can develop abnormalities in all of these organs in addition to hyperglycaemia [ 19 ], the symptoms of which often precede the diabetes. They can be characterized by pancreas hypoplasia resulting in beta-cell dysfunction and reduced insulin secretion [ 21 ]. About 50% of the patients present with hypomagnesaemia and hypokalaemia as well [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Analysis of Hungarian MODY Patients—Part I: Gene Panel Sequencing Reveals Pathogenic Mutations in HNF1A, HNF1B, HNF4A, ABCC8 and INS Genes

Gaál

Szücs

Kántor

et al. 2021

Life

Self Cite

View full text Add to dashboard Cite

Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment.

show abstract

Monogenic Forms of Diabetes Mellitus

Cited by 15 publications

References 220 publications

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Modeling Maturity Onset Diabetes of the Young in Pluripotent Stem Cells: Challenges and Achievements

A Comprehensive Analysis of Hungarian MODY Patients—Part I: Gene Panel Sequencing Reveals Pathogenic Mutations in HNF1A, HNF1B, HNF4A, ABCC8 and INS Genes

Contact Info

Product

Resources

About