The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients

Ivanoshchuk, D.; Shakhtshneider, E.; Rymar, O. D.; Ovsyannikova, Alla; Михайлова, С. В.; Fishman, Veniamin; Валеев, Э. С.; Орлов, П. С.; Воевода, М. И.

doi:10.3390/jpm11010057

Cited by 14 publications

(12 citation statements)

References 57 publications

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“…The most common forms of monogenic diabetes share residual insulin secretion, leading to the detection of C-peptide, which distinguishes MODY from severe type 1 diabetes. To date, at least 14 MODY subtypes have been identified depending on specific variants, including GCK , HNF4A , HNF1A , and others ( 7 ). In patients with MODY, the most frequently mutated gene is GCK ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

et al. 2021

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BackgroundWe aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment.MethodA Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing.ResultsThe proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5–12.1%) and fasting blood glucose (FBG, 91.4–189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G>A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 μmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives.ConclusionThis study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.

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Section: Introductionmentioning

confidence: 99%

Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

et al. 2021

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“…It shows a different clinical heterogeneity due to its different mutation genes, therefore, disease judgment, prognosis, and treatment are also different ( 4 ). So far, 14 MODY-related genes have been discovered, including KCNJ11 , ABCC8 , INS , GCK , IPF1 , PTF1A , GLIS3 , FOX3 , EIF2AK3 , GLUT2 , HNF1A , HNF1B , HNF4A , and PAX4 ( 5 – 9 ). Among these genes, heterozygous mutations in HNF1A , HNF4A , and GCK have been identified as the root cause of more than 90% of MODY cases ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Precision Therapy for a Chinese Family With Maturity-Onset Diabetes of the Young

Shu

Wang

et al. 2021

Front. Endocrinol.

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ObjectiveTo determine the pathogenic gene and explore the clinical characteristics of maturity-onset diabetes of the young type 2 (MODY2) pedigree caused by a mutation in the glucokinase (GCK) gene.MethodsUsing whole-exome sequencing (WES), the pathogenic gene was detected in the proband—a 20-year-old young man who was accidentally found with hyperglycemia, no ketosis tendency, and a family history of diabetes. The family members of the proband were examined. In addition, relevant clinical data were obtained and genomic DNA from peripheral blood was obtained. Pathologic variants of the candidate were verified by Sanger sequencing technology, and cosegregation tests were conducted among other family members and non-related healthy controls. After adjusting the treatment plan based on the results of genetic testing, changes in biochemical parameters, such as blood glucose levels and HAblc levels were determined.ResultsIn the GCK gene (NM_000162) in exon 9, a heterozygous missense mutation c.1160C > T (p.Ala387Val) was found in the proband, his father, uncle, and grandmother. Thus mutation, which was found to co-segregate with diabetes, was the first discovery of such a mutation in the Asian population. After stopping hypoglycemic drug treatment, good glycemic control was achieved with diet and exercise therapy.ConclusionGCK gene mutation c.1160C > T (p.Ala387Val) is the pathogenic gene in the GCK-MODY pedigree. Formulating an optimized and personalized treatment strategy can reduce unnecessary excessive medical treatment and adverse drug reactions, and maintain a good HbA1c compliance rate

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“…Дебют MODY чаще всего является бессимптомным, отсутствуют клинические проявления гипергликемии, в связи с чем заболевание нередко бывает случайной находкой в ходе скрининга [26]. В настоящее время известно 14 подтипов MODY, в России наиболее часто встречается подтип MODY, обусловленный мутацией в гене глюкокиназы (GCK-MODY) [27].…”

Section: Introductionunclassified

Maturity-Onset Diabetes of the Young and the Structure of Gestational Diabetes Mellitus

Belyaeva¹,

Ovsyannikova²,

Rymar³

2021

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Objective of the Review: To systematise the information on MODY (Maturity-Onset Diabetes of the Young) during pregnancy. Key Points. MODY in pregnant patients should be distinguished from typical gestational diabetes mellitus, since these conditions require early pregnancy management. The article discusses combined criteria for differential diagnosis of types of diabetes mellitus in pregnancy and indications for molecular genetic testing. We describe clinical cases demonstrating the dependence of pregnancy outcomes on whether the foetus inherits the mutation or not. Also, the article describes the outlooks of non-invasive diagnosis of mutation status of the foetus and possible modification of therapy depending on the result. Conclusion. Diagnosis and therapy of MODY is a burning issue since there are no algorithms and the clinical experience is quite sparse. Keywords: MODY, gestational diabetes mellitus, GCK-MODY, HNF1A-MODY.

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The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients

Cited by 14 publications

References 57 publications

Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

Precision Therapy for a Chinese Family With Maturity-Onset Diabetes of the Young

Maturity-Onset Diabetes of the Young and the Structure of Gestational Diabetes Mellitus

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