Molecular-genetic verification and treatment of neonatal diabetes mellitus related to the defects in ATP-dependent potassium channels: Results of the observation of 9 patients and the first description of ABCC8 gene mutations in Russia

2011 ◽  
Vol 57 (2) ◽  
pp. 3-8
Author(s):  
I I Dedov ◽  
Iu V Tikhonovich ◽  
Elena E Petriaikina ◽  
I G Rybkina ◽  
I É Volkov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Beta Cells ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Molecular Genetic Analysis ◽  
Neonatal Diabetes Mellitus ◽  
Molecular Genetic Study ◽  
Abcc8 Gene ◽  
Sound Therapy

Introduction of the methods for molecular-genetic analysis into clinical practice has opened up new prospects for both diagnosis and pathogenetically sound therapy of neonatal diabetes mellitus. It is currently known that the overwhelming majority of the cases of diabetes mellitus developing in children during the first six month of life are associated with defects of the genes controlling formation, development, and functional activity of pancreatic beta-cells whereas type 1 diabetes mellitus of autoimmune origin accounts for less than 1% of this pathology. This paper reports the results of a molecular-genetic study of 14 patients presenting with neonatal diabetes mellitus. Nine cases are shown to have developed as a result of mutations in KCNJ11 and ABCC8 genes. ABCC8 mutations are described for the first time in Russia. Analysis of clinical forms of neonatal diabetes mellitus revealed correlation between the type of mutations, clinical features of the disease, and susceptibility of the patients to sulfonylurea drugs.

The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

2020 ◽  
Vol 33 (12) ◽  
pp. 1605-1608
Author(s):  
Xiao Qin ◽  
Jingzi Zhong ◽  
Dan Lan
Keyword(s):  
Diabetes Mellitus ◽  
Novel Mutation ◽  
Male Infant ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Rare Form ◽  
Case Presentation ◽  
Abcc8 Gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

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

scholarly journals Genetic Analysis and Follow-Up of 25 Neonatal Diabetes Mellitus Patients in China

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Bingyan Cao ◽  
Chunxiu Gong ◽  
Di Wu ◽  
Chaoxia Lu ◽  
Fang Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Analysis ◽  
Neonatal Diabetes ◽  
Molecular Genetic Analysis ◽  
Neonatal Diabetes Mellitus ◽  
Chinese Patients ◽  
Genetic Etiology ◽  
Good Glycemic Control ◽  
Polygenic Inheritance

Aims.To study the clinical features, genetic etiology, and the correlation between phenotype and genotype of neonatal diabetes mellitus (NDM) in Chinese patients.Methods.We reviewed the medical records of 25 NDM patients along with their follow-up details. Molecular genetic analysis was performed. We compared the HbA1c levels between PNDM group and infantile-onset T1DM patients.Results.Of 25 NDM patients, 18 (72.0%) were PNDM and 7 (28.0%) were TNDM. Among 18 PNDM cases, 6 (33.3%) had known KATP channel mutations (KATP-PNDM). There were six non-KATP mutations, five novel mutations, includingINS,EIF2AK3(n=2),GLIS3, andSLC19A2, one knownEIF2AK3mutation. There are twoABCC8mutations in TNDM cases and one paternal UPD6q24. Five of the six KATP-PNDM patients were tried for glyburide transition, and 3 were successfully switched to glyburide. Mean HbA1c of PNDM was not significantly different from infantile onset T1DM (7.2% versus 7.4%,P=0.41).Conclusion.PNDM accounted for 72% of NDM patients. About one-third of PNDM and TNDM patients had KATP mutations. The genetic etiology could be determined in 50% of PNDM and 43% of TNDM cases. PNDM patients achieved good glycemic control with insulin or glyburide therapy. The etiology of NDM suggests polygenic inheritance.

scholarly journals A Case of Transient Neonatal Diabetes Mellitus Attributable to a Nonspecific Mutation in the ABCC8 Gene

2021 ◽  
Vol 27 (2) ◽  
pp. 121-124
Author(s):  
Won Seob Shin ◽  
Hwal Rim Jeong ◽  
Ji Won Koh
Keyword(s):  
Diabetes Mellitus ◽  
Early Adulthood ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Clinical Form ◽  
Abcc8 Gene ◽  
Type 2 Dm ◽  
Chromosome 6Q24 ◽  
Transient Neonatal Diabetes

Neonatal diabetes mellitus (NDM) is defined as hyperglycemia that persists for more than 2 weeks and requires insulin therapy. NDM principally occurs before 6 months of age. Transient NDM (TNDM) is a clinical form of NDM that persists for a median of 12 weeks and resolves completely by 18 months. However, it may relapse as type 2 DM during early adulthood. The major causes of TNDM are mutations in chromosome 6q24 or the KCNJ11 or ABCC8 genes; the latter encode the two subunits of the pancreatic adenosine triphosphate (ATP)-sensitive potassium channel (KATP-channel). This condition responds well to oral sulfonylurea therapy. Herein, we report a neonate who was small for gestational age and exhibited TNDM symptoms. Genetic analysis revealed a nonspecific mutation in ABCC8; he was successfully treated with oral sulfonylurea.

A Novel c.125 T>G (p.Val42Gly) Mutation in The Human INS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin Synthesis

2018 ◽  
Vol 128 (03) ◽  
pp. 182-189
Author(s):  
Fei Sun ◽  
Wenhua Du ◽  
Junhua Ma ◽  
Mingjun Gu ◽  
Jingnan Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Culture ◽  
Pancreatic Beta Cells ◽  
Culture Medium ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Open Reading Frame ◽  
Heterozygous Mutation ◽  
Cell Culture Medium ◽  
Reading Frame

Abstract Background Neonatal diabetes mellitus is likely caused by monogenic mutations, several of which have been identified. INS mutations have a broad spectrum of clinical presentations, ranging from severe neonatal onset to mild adult onset, which suggests that the products of different mutant INS alleles behave differently and utilize distinct mechanisms to induce diabetes. In this study, a neonatal diabetes mellitus patient’s INS gene was sequenced, and functional experiments were conducted. Methods The neonatal diabetes mellitus patient’s genomic DNA was extracted, and the patient’s KCNJ11, ABCC8, and INS genes were sequenced. A novel mutation was identified in INS, and the open reading frame of this human mutant INS gene was inserted into the pMSCV-PIG plasmid. The constructed pMSCV-PIG plasmid was combined with VSV-g and Gag-pol and transfected into 293T cells to package the lentivirus. To stably overexpress the mutant gene, INS-1 cells were infected with the virus. The levels of insulin in the cell culture medium and cytoplasm were determined by ELISA and immunocytochemistry, respectively. Results A heterozygous mutation, c.125T>G (p. Val42Gly), was identified in a neonatal diabetes mellitus patient’s INS gene. The human mutant INS open reading frame was overexpressed in INS-1 cells, and the mutant insulin was undetectable in the cell culture medium and cytoplasm. Conclusions The novel heterozygous activating mutation c.125 T>G (p.Val42Gly) impairs the synthesis of insulin by pancreatic beta cells, resulting in diabetes.

Neonatal Diabetes Mellitus Due to a Novel ABCC8 Gene Mutation Mimicking an Organic Acidemia

2013 ◽  
Vol 81 (7) ◽  
pp. 702-704 ◽  
Author(s):  
Akanksha N. Thakkar ◽  
Mamta N. Muranjan ◽  
Sunil Karande ◽  
Nalini S. Shah
Keyword(s):  
Diabetes Mellitus ◽  
Gene Mutation ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Organic Acidemia ◽  
Abcc8 Gene

scholarly journals Successful sulfonylurea treatment of a neonate with neonatal diabetes mellitus due to a novel missense mutation, p.P1199L, in the ABCC8 gene

2012 ◽  
Vol 32 (8) ◽  
pp. 645-647 ◽  
Author(s):  
O Oztekin ◽  
E Durmaz ◽  
S Kalay ◽  
S E Flanagan ◽  
S Ellard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Missense Mutation ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Abcc8 Gene

scholarly journals A case of a Japanese patient with neonatal diabetes mellitus caused by a novel mutation in the ABCC8 gene and successfully controlled with oral glibenclamide

2015 ◽  
Vol 24 (4) ◽  
pp. 191-193 ◽  
Author(s):  
Ryojun Takeda ◽  
Masaki Takagi ◽  
Kentaro Miyai ◽  
Hiroyuki Shinohara ◽  
Hiroko Yagi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Japanese Patient ◽  
Novel Mutation ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Abcc8 Gene
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