scholarly journals Monogenic Diabetes due to ABCC8/KCNJ11 Mutation: Case Study and Review of Literature

2020 ◽  
Author(s):  
Gul Bano
Keyword(s):  
Single Gene ◽  
Adult Population ◽  
Early Adulthood ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Effective Manner ◽  
Kcnj11 Gene ◽  
Mitochondrial Diabetes ◽  
The Family

Monogenic diabetes arises due to mutation in a single-gene and is recognized by their striking familial inheritance pattern. This form of diabetes is inherited in an autosomal dominant or recessive fashion, unlike polygenic Type 1 (autoimmune) or type 2 diabetes caused by the combined action of more than one gene [1-11]. Monogenic diabetes is classified into three main groups: Neonatal diabetes mostly presents in the first six months of birth, maturity onset diabetes of the young (MODY) and maternally inherited mitochondrial diabetes. These mutations run in the family and have a predictable course. Most of the monogenic diabetes is treated with oral medications like sulfonylurea rather than insulin. ABCC8/KCNJ11 gene mutations also cause monogenic diabetes. This gene mutation has been found in ~50% of congenital hyperinsulinemia (CHI) patients. In such cases diabetes commonly presents in the neonatal period (transient or permanent) or at adolescence / early adulthood [1]. We present a 58-year-old diabetic lady, who was detected with ABCC8 mutation during the cascade testing [8]. She was diagnosed with diabetes at the age of 12 [8]. Her son had history of neonatal hypoglycaemia and developed diabetes at the age of 15. He was the index case who was found to have ABCC8 mutation. The family has several other members diagnosed with diabetes. The aim of the article is to increase awareness and understanding of monogenic diabetes among the medical practitioners in adult population with diabetes so that the genetic testing can be offered in a cost effective manner.

Detection of KCNJ11 Gene Mutations in a Family with Neonatal Diabetes Mellitus

2012 ◽  
Vol 16 (2) ◽  
pp. 109-114 ◽  
Author(s):  
Farzaneh Abbasi ◽  
Sadaf Saba ◽  
Azadeh Ebrahim-Habibi ◽  
Forough A. Sayahpour ◽  
Parvin Amiri ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Kcnj11 Gene

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

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.

scholarly journals Monogenic diabetes mellitus and clinical implications of genetic diagnosis

2021 ◽  
Vol 5 (3) ◽  
pp. 106-116
Author(s):  
Eungu Kang ◽  
Lindsey Yoojin Chung ◽  
Yu Jin Kim ◽  
Kyung Eun Oh ◽  
Young-Jun Rhie
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Clinical Implications ◽  
High Dose ◽  
Activating Mutations ◽  
Β Cell Function

Monogenic diabetes mellitus, which is diabetes caused by a defect in a single gene that is associated with β cell function or insulin action, accounts for 1% to 6% of all pediatric diabetes cases. Accurate diagnosis is important, as the effective treatment differs according to genetic etiology in some types of monogenic diabetes: high-dose sulfonylurea treatment in neonatal diabetes caused by activating mutations in KCNJ11 or ABCC8; low-dose sulfonylurea treatment in HNF1A/HNF4A-diabetes; and no treatment in GCK diabetes. Monogenic diabetes should be suspected by clinicians for certain combinations of clinical features and laboratory results, and approximately 80% of monogenic diabetes cases are misdiagnosed as type 1 diabetes or type 2 diabetes. Here, we outline the types of monogenic diabetes and the clinical implications of genetic diagnosis.

scholarly journals A RARE CASE OF A YOUNG INFANT WITH MONOGENIC DIABETES MELLITUS AND CENTRAL VENOUS SINUS THROMBOSIS

2020 ◽  
pp. 32-33
Author(s):  
Payal Patil ◽  
Rajesh Kulkarni ◽  
Aarti Kinikar
Keyword(s):  
Diabetes Mellitus ◽  
Autosomal Dominant ◽  
Sinus Thrombosis ◽  
Single Gene ◽  
Young Infant ◽  
Neonatal Diabetes ◽  
Female Child ◽  
Monogenic Diabetes ◽  
Permanent Neonatal Diabetes ◽  
Glucose Levels

Diabetes mellitus is a metabolic disease characterised by chronically high glucose levels. Genetic factors have been implicated in the etiology following mutations in a single gene. An extremely rare form of diabetes mellitus is monogenic diabetes, a subset of which is permanent neonatal diabetes which is usually suspected in a child less than 6 months presenting with hyperglycaemia. We are reporting case of a 40 days old female child with an autosomal dominant INS gene mutation which results in permanent neonatal diabetes in infants requiring lifelong insulin therapy.

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 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 Novel Perspectives of Super-High Dose Glybenclamide in an Infant With DEND Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A453-A453
Author(s):  
Galia Barash ◽  
Haim Bassan ◽  
Livne Ayelet ◽  
Lilach Benyamini ◽  
Eli Heyman ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Glucose Monitoring ◽  
Gene Mutations ◽  
Missense Variant ◽  
Neonatal Diabetes ◽  
Heterozygous Mutation ◽  
High Dose ◽  
Kcnj11 Gene ◽  
High Doses

Abstract Mutations in KCNJ11 gene cause a variety of persistent neonatal diabetes mellitus syndromes (PNDM), with and without developmental delay and epilepsy presentations (developmental delay, epilepsy, and neonatal diabetes - DEND Syndrome). We report a heterozygous mutation for pathogenic KCNJ11 missense variant: c.190G>A, p. (Val64Met), reported once so far, associated with severe epilepsy and neurological deterioration phenotype, responsive to a combination of super high doses of Glibenclamide (Sulfonylurea) and oral steroids. We had the patient attached to continuous glucose monitoring, performed electroencephalogramic tracings, magnetic resonance imaging and whole exome sequencing on parents and patient DNA and Sanger sequencing (SS) on candidate gene mutations. His phenotypic description and management during 18 months, demonstrates this mutation is responsive to super-high doses of SU combined with high dose 6 weeks steroids protocol. In conclusion, we have identified a de novo heterozygous missense mutation as the etiology for severe DEND syndrome in a one day old neonate, presenting with asymptomatic hyperglycemia, responsive to a novel management combination.

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