Monogenic forms of diabetes resulting from β‎ cell dysfunction

2011 ◽  
pp. 1754-1759
Author(s):  
Rachel Besser ◽  
Andrew Hattersley
Keyword(s):  
Clinical Phenotype ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Monogenic Disorders ◽  
Cell Dysfunction ◽  
Onset Diabetes ◽  
Monogenic Forms Of Diabetes ◽  
Clinical Category

Monogenic diabetes refers to diabetes resulting from mutations in a single gene. This chapter discusses monogenic disorders causing β‎ cell dysfunction, which accounts for the majority of cases of monogenic diabetes. Patients can usually be divided into three clinical categories: maturity-onset diabetes of the young (MODY), which is dominantly inherited familial diabetes; neonatal diabetes, diagnosed under the age of 6 months; and monogenic diabetes syndromes, which are characterized by multiple nonpancreatic features. In each clinical category, there are several aetiological genes that usually result in a discrete clinical phenotype.

scholarly journals Heterozygous RFX6 protein truncating variants are associated with Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance

2017 ◽  
Author(s):  
Kashyap A Patel ◽  
Jarno Kettunen ◽  
Markku Laakso ◽  
Alena Stančáková ◽  
Thomas W Laver ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Gastric Inhibitory Polypeptide ◽  
Monogenic Diabetes ◽  
Human Pancreas ◽  
Maturity Onset Diabetes ◽  
Discovery Cohort ◽  
Cell Dysfunction ◽  
Onset Diabetes ◽  
Reduced Penetrance ◽  
And Function

AbstractFinding new genetic causes of monogenic diabetes can help to understand development and function of the human pancreas. We aimed to find novel protein–truncating variants causing Maturity–Onset Diabetes of the Young (MODY), a subtype of monogenic diabetes. We used a combination of next–generation sequencing of MODY cases with unknown aetiology along with comparisons to the ExAC database to identify new MODY genes. In the discovery cohort of 36 European patients, we identified two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants were enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio, OR=131, P=l×l0‐4). We found similar results in non–Finnish European (n=348, OR=43, P=5×l0‐5) and Finnish (n=80, OR=22, P=1×l0‐6) replication cohorts. The overall meta–analysis OR was 34 (P=l×l0‐16). RFX6 heterozygotes had reduced penetrance of diabetes compared to common HNF1A and HNF4A–MODY mutations (27%, 70% and 55% at 25 years of age, respectively). The hyperglycaemia resulted from beta–cell dysfunction and was associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.

Monogenic Diabetes Mellitus: Neonatal Diabetes and Maturity-Onset Diabetes of the Young

2021 ◽  
pp. 279-298
Author(s):  
Siri Atma W. Greeley ◽  
Mary K. McCauley ◽  
Louis H. Philipson ◽  
Mark A. Sperling
Keyword(s):  
Diabetes Mellitus ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

scholarly journals MOLECULAR GENETICS AND CLINICAL ASPECTS OF MONOGENIC DIABETES MELLITUS

2012 ◽  
Vol 67 (1) ◽  
pp. 81-86 ◽  
Author(s):  
V. A. Peterkova ◽  
T. L. Kuraeva ◽  
S. A. Prokof’ev ◽  
A. O. Emel'yanov ◽  
E. Yu. Zakharova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Genetics ◽  
Neonatal Diabetes ◽  
Clinical Results ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Clinical Aspects ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Didmoad Syndrome

The paper is dedicated to clinical and laboratory aspects of Diabetes Mellitus non-immune forms, such as neonatal Diabetes Mellitus, Maturity Onset Diabetes of young (MODY), DIDMOAD-syndrome, Wolframe syndrome, Alstrom syndrome and its determinating genes. The analysis of proper clinical results are present in this paper.

scholarly journals Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 117
Author(s):  
Antonella Marucci ◽  
Irene Rutigliano ◽  
Grazia Fini ◽  
Serena Pezzilli ◽  
Claudia Menzaghi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Precision Medicine ◽  
Genetic Disorder ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Patients With Diabetes ◽  
Clinical Strategy

Monogenic diabetes is a genetic disorder caused by one or more variations in a single gene. It encompasses a broad spectrum of heterogeneous conditions, including neonatal diabetes, maturity onset diabetes of the young (MODY) and syndromic diabetes, affecting 1–5% of patients with diabetes. Some of these variants are harbored by genes whose altered function can be tackled by specific actions (“actionable genes”). In suspected patients, molecular diagnosis allows the implementation of effective approaches of precision medicine so as to allow individual interventions aimed to prevent, mitigate or delay clinical outcomes. This review will almost exclusively concentrate on the clinical strategy that can be specifically pursued in carriers of mutations in “actionable genes”, including ABCC8, KCNJ11, GCK, HNF1A, HNF4A, HNF1B, PPARG, GATA4 and GATA6. For each of them we will provide a short background on what is known about gene function and dysfunction. Then, we will discuss how the identification of their mutations in individuals with this form of diabetes, can be used in daily clinical practice to implement specific monitoring and treatments. We hope this article will help clinical diabetologists carefully consider who of their patients deserves timely genetic testing for monogenic diabetes.

An analysis of the sequence of the BAD gene among patients with maturity-onset diabetes of the young (MODY)

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Karolina Antosik ◽  
Piotr Gnyś ◽  
Przemysława Jarosz-Chobot ◽  
Małgorzata Myśliwiec ◽  
Agnieszka Szadkowska ◽  
...  
Keyword(s):  
Genetic Screening ◽  
Sanger Sequencing ◽  
Single Gene ◽  
Gene Mutations ◽  
Paediatric Population ◽  
Monogenic Diabetes ◽  
Diabetic Patients ◽  
Molecular Testing ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

AbstractBackground:Monogenic diabetes is a rare disease caused by single gene mutations. Maturity onset diabetes of the young (MODY) is one of the major forms of monogenic diabetes recognised in the paediatric population. To date, 13 genes have been related to MODY development. The aim of the study was to analyse the sequence of the BCL2-associated agonist of cell death (Methods:A group of 122 diabetic patients were recruited from the “Polish Registry for Paediatric and Adolescent Diabetes – nationwide genetic screening for monogenic diabetes” project. The molecular testing was performed by Sanger sequencing.Results:A total of 10 sequence variants of theConclusions:Among the analysed patients suspected of MODY, one possible pathogenic variant was identified in one patient; however, further confirmation is required for a certain identification.

scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options

Endocrines ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 485-501
Author(s):  
Zoltan Antal
Keyword(s):  
Clinical Presentation ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Inappropriate Treatment ◽  
Monogenic Forms Of Diabetes ◽  
Initial Description

Maturity Onset Diabetes of the Young (MODY) encompasses a group of rare monogenic forms of diabetes distinct in etiology and clinical presentation from the more common forms of Type 1 (autoimmune) and Type 2 diabetes. Since its initial description as a clinical entity nearly 50 years ago, the underlying genetic basis for the various forms of MODY has been increasingly better elucidated. Clinically, the diagnosis may be made in childhood or young adulthood and can present as overt hyperglycemia requiring insulin therapy or as a subtle form of slowly progressive glucose impairment. Due to the heterogeneity of clinical symptoms, patients with MODY may be misdiagnosed as possessing another form of diabetes, resulting in potentially inappropriate treatment and delays in screening of affected family members and associated comorbidities. In this review, we highlight the various known genetic mutations associated with MODY, clinical presentation, indications for testing, and the treatment options available.

Neonatal Diabetes – From Gene Discovery yo Clinical Practice Changes

2013 ◽  
Vol 20 (3) ◽  
pp. 343-352
Author(s):  
Cristian Guja ◽  
Loreta Guja ◽  
Constantin Ionescu-Tîrgovişte
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Special Focus ◽  
Sulphonylurea Treatment ◽  
The Common

Abstract Diabetes mellitus is one of the most common chronic diseases but also one of the most heterogeneous. Apart the common phenotypes of type 1 and type 2 diabetes, around 1-2% of all cases arise from a single gene mutation and are known as monogenic diabetes. Diabetes diagnosed within the first 6 months of life is known as neonatal diabetes and has been extensively studied during the last two decades. Unraveling the genetic cause and molecular mechanism of this rare diabetes phenotype led to a dramatic change in the treatment of these children who often can be switched from insulin to sulphonylurea treatment. The aim of this paper is to review the known genetic causes of neonatal diabetes and to highlight the most recent aspects of the disease caused by mutations in the KATP and insulin genes, with a special focus on the individualized treatment of these cases

scholarly journals Mutations at the BLK locus linked to maturity onset diabetes of the young and  -cell dysfunction

2009 ◽  
Vol 106 (34) ◽  
pp. 14460-14465 ◽  
Author(s):  
M. Borowiec ◽  
C. W. Liew ◽  
R. Thompson ◽  
W. Boonyasrisawat ◽  
J. Hu ◽  
...  
Keyword(s):  
Maturity Onset Diabetes ◽  
Cell Dysfunction ◽  
Onset Diabetes

Monogenic Diabetes Not Caused By Mutations in Mody Genes: A Very Heterogenous Group of Diabetes

2017 ◽  
Vol 126 (10) ◽  
pp. 612-618 ◽  
Author(s):  
Zeynep Şıklar ◽  
Elisa de Franco ◽  
Matthew Johnson ◽  
Sarah Flanagan ◽  
Sian Ellard ◽  
...  
Keyword(s):  
Immune System ◽  
Beta Cells ◽  
Age Of Onset ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Pediatric Endocrinology ◽  
Immune System Dysfunction ◽  
Heterogenous Group ◽  
Type 1 Dm

AbstractMonogenic diabetes represents a heterogeneous group of disorders resulting from a single gene defect leading to disruption of insulin secretion or a reduction in the number of beta cells. Despite the classification of monogenic diabetes into neonatal diabetes or maturity onset diabetes of the young (MODY) according to age of onset, not every case can be classified into those 2 groups. We evaluated patients with monogenic diabetes diagnosed during the last 10 year period. Type 1 DM, MODY, and patients with negative autoantibodies and no mutation in a known gene were excluded from the study. Thirteen patients were diagnosed with monogenic diabetes in Department of Pediatric Endocrinology, Ankara University School of Medicine, Ankara, Turkey. Five of them were diagnosed after 6 months of age. Five had a KATP channel defect. Mutations in genes resulting in destruction of beta cells were detected in 7 patients, with 4 cases having a WFS, 2 an LRBA, and one a IL2RA mutation. Additional systemic findings were seen in 6/13 patients, with 5/6 having severe immune system dysfunction. Treatment with sulphonylurea was successful in two patients.. The other patients were given insulin in differing doses. Four patients died during follow-up, three of which had immune system dysfunction. Monogenic diabetes can be diagnosed after 6 months of age, even with positive autoantibodies. Immune dysfunction was a common feature in our cohort and should be investigated in all patients with early-onset monogenic diabetes. Mortality of patients with monogenic diabetes and additional autoimmunity was high in our cohort and is likely to reflect the multisystem nature of these diseases.

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