Maturity-onset Diabetes Of The Young Type 3 Research Articles

Hepatocellular Adenoma: Report of 2 Cases That Highlight the Relevance of Phenotype-Genotype Correlation in the Pediatric Population.

Hepatocellular adenoma (HCA) in the pediatric population is very rare and there are only limited studies, especially with molecular characterization of the tumors. Main HCA subtypes recognized in the current WHO classification include HNF1A-inactivated HCA (H-HCA), inflammatory HCA (IHCA), β-catenin-activated HCA (b-HCA), and β-catenin-activated IHCA (b-IHCA) and sonic hedgehog HCA (shHCA) is reported as an emerging subtype. Clinical history, pathological information, and molecular studies for a series of 2 cases of pediatric HCA were reviewed. Case 1 was a b-HCA characterized by somatic CTNNB1 S45 mutation in a 11-year-old male with Abernethy malformation. Case 2 was a H-HCA characterized by germline HNF1A variant (c.526+1G>A) in a 15-year-old male associated with maturity-onset diabetes of the young type 3 (MODY3). Our findings highlight the rarity of these 2 cases associated with adenomatosis, and the contribution of molecular/genetic analysis for proper sub-typing, prognosis and family surveillance.

De novo HNF1A mutation of young maturity-onset diabetes 3 of a young girl—Case report

Young maturity-onset diabetes of the young type3(MODY3) as a special type of diabetes, the probability of diagnosis is low. This article reports on a case and reviews the relevant knowledge of the disease. We report an 11-year-and-11-month-old girl whose grandmother died from diabetic complications while the rest of the families were non-diabetes. The proband was initially treated with insulin and metformin but the threatment proved inefficient. After an exome-targeted capture sequencing test, she was diagnosed with mature-onset diabetes of young type 3 (MODY3), and sulfonylureas make sense. The key to mody treatment is a correct and timely diagnosis, which contributes to helping patients overcome the problems of MODY3, especially for blood sugar control.

Maturity-Onset Diabetes of the Young (MODY) in Pregnancy: A Review.

Hyperglycaemia in pregnancy is one of the most common complications of pregnancy and is generally diagnosed as gestational diabetes mellitus (GDM). Nevertheless, clinical symptoms of hyperglycaemia in pregnancy in some cases does not match the clinical manifestations of GDM. It is suspected that 1-2% of women diagnosed with GDM are in fact misdiagnosed maturity-onset diabetes of the young (MODY). MODY has often subclinical course, thus it is challenging for clinicians to aptly diagnose monogenic diabetes in pregnancy. Proper diagnosis is crucial for the effective treatment of hyperglycaemia in pregnancy. Many studies revealed that misdiagnosis of MODY increases the rate of complications for both mother and fetus. This review of literature reports the current knowledge of diagnosis, treatment and complications of the most common types of MODY in pregnancy.

A clinical mutation in glucokinase causing maturity-onset diabetes in the young type 2 increases enzyme activity.

Glucokinase (GCK) is the pancreatic β-cell glucose sensor, and its kinetics are key to that purpose. A slow transition step, displayed as non-hyperbolic kinetics, and a low affinity for glucose characterize GCK. Mutations in GCK associated with maturity-onset diabetes of the young type 2 (MODY2) previously describedreduce the functionality of the human pancreatic β-cell, leading to diabetic clinical phenotypes. We present a kinetic characterization of the G448D mutation identified in a MODY2 patient, which is one of the first mutations to exhibit increased functionality. This mutant displays increased activity, high affinity for both Mg2+ -ATP and glucose, hyperbolic kinetics and increased phosphorylation potential. Hyperbolic kinetics and assays in the presence of glycerol indicate that G448D lacks the slow transition step crucial for the pancreatic β-cell glucose sensor function.

17q12 Microdeletion Syndrome as a Rare Cause of Elevated Liver Enzymes: Case Report and Literature Review

17q12 deletion syndrome is a rare autosomal dominant inherited condition. It results from de novo mutation and can occur without a family history. Hepatocyte nuclear factor-1 beta (HNF1B) and LIM homeobox 1 (LXH1) genes are the most common genes to be deleted in this syndrome. It has unique clinical characteristics involving multiple systems in the body. The most common presentations are usually renal involvement and maturity-onset diabetes of the young type 5 (MODY5). Genetic study is the golden tool to diagnose patients with this syndrome. Our case presents the unique clinical features of 17q12 deletion syndrome along with a literature review.

Genetic predisposition to gestational diabetes mellitus in the Kazakh population

Background and aimsThe purpose of the study was to conduct a comparative analysis of population frequencies of alleles and genotypes of polymorphic variants of genes for impaired insulin synthesis and associated with insulin signal transduction. MethodsThis investigation uses a genomic database of 1800 conditionally healthy individuals of Kazakh ethnicity, who underwent full genome genotyping using OmniChip 2.5–8 Illumina chips of ∼2.5 million Single Nucleotide Polymorphism at deCODE Iceland Genomic Centre. ResultsThe highest frequency of carriage of minor A allele – 17.6% rs4607517 polymorphism of Glucokinase gene, unfavorable genotypes A/G – 29.5% and A/A – 3.0% in comparison with European and Asian populations, indicates a contribution of hereditary family forms of Maturity-onset diabetes of the young type 2 to gestational diabetes mellitus in Kazakh population. ConclusionsThe study of the associations of genetic markers of gestational diabetes mellitus will allow timely identification of high-risk groups before and at an early stage of pregnancy, carrying out the necessary effective preventive measures and, in the case of gestational diabetes mellitus development, optimizing the correction of carbohydrate metabolism disorders and predicting outcomes for the mother and the fetus.

ODP255 Woman With Maturity-Onset Diabetes of the Young Type 2 (MODY2) Mistakenly Diagnosed and Treated as Type 2 Diabetes Mellitus

Abstract Background MODY2 is a rare, monogenic form of diabetes, caused by mutations in the glucokinase gene (GCK), and is often misclassified as type 2 diabetes. Clinical case: A 37-year-old woman, during childhood, at the age of 9, was characterized as overweight and had a poor diet, despite being physically active. Her pediatrician diagnosed her with DM2 and started treatment with metformin. However, there was no improvement in fasting glucose levels, so the family decided to stop the medication on their own. In 2008, the patient became pregnant, presenting fasting glucose levels between 120-130 mg/dl (n<99 mg/dl), and continued without hypoglycemic treatment. In 2010, she resumed treatment for glycemic control having used: metformin, sulphonylurea, IDDP4, and basal insulin. Despite the various treatments tested, there was altered fasting glycemia, in the 130mg/dl range. In 2012, she increased her physical activity by training for a half marathon run. At the peak of her form, but maintaining hyperglycemia (always measuring while fasting), she started liraglutide 1.8mg. In 2019, she presented episodes of malaise during training, being indicated by her physician, to discontinue liraglutide, then starting dapagliflozin, but there was still no improvement of blood glucose levels. In August 2019, she was instructed to take the following medications: insulin degludec, liraglutide, and dapagliflozin. Current weight was 53kg, height 1,57cm and a BMI 21,5kg/. Laboratory exams were requested with the following results: A1C 6,6% (n: <5,7%), mean glycemia 143mg/dL (n: 70-99 mg/dL), fasting glycemia 127mg/dL (n: <100mg/dL), urea 24mg/dL (n: 13-43 mg/dL), creatinine 0,83mg/dL (n: 0,8-1,3 mg/dL), AST 16U/L (n: 10-34 U/L), ALT 17U/L (n 10-130 U/L), LDL 109mg/dL (n<100mg/dl), HDL 80mg/dL (n>60 mg/dL), TG 90mg/dL (n<150 mg/dL), total cholesterol 207mg/dL (<200 mg/dL). Faced with the suspicion of diabetes with different behavior than DM1 and DM2, genetic testing was requested for confirmation. In September 2019, the result arrived, pointing out a genetic change in heterozygosis in the GCK gene. This is a rare mutation that results in the depletion of the phenylalanine amino acid at position 150 of the protein glucokinase. This result confirmed the diagnose of MODY type 2. The patient was oriented to discontinue anti-hyperglycemic agents, maintain a low glycemic index diet, and daily physical exercises. Thus, she has been maintaining excellent glycemic control and adequate weight. Conclusion Suspicion and characterization of MODY through clinical history, and confirmation of diagnosis through genetic testing, is essential to avoid unnecessary or inefficient treatments, and to ensure a better quality of life for the patient. Presentation: No date and time listed

Novel Loss-of-Function Variant in HNF1a Induces β-Cell Dysfunction through Endoplasmic Reticulum Stress.

Heterozygous variants in the hepatocyte nuclear factor 1a (HNF1a) cause MODY3 (maturity-onset diabetes of the young, type 3). In this study, we found a case of novel HNF1a p.Gln125* (HNF1a-Q125ter) variant clinically. However, the molecular mechanism linking the new HNF1a variant to impaired islet β-cell function remains unclear. Firstly, a similar HNF1a-Q125ter variant in zebrafish (hnf1a+/-) was generated by CRISPR/Cas9. We further crossed hnf1a+/- with several zebrafish reporter lines to investigate pancreatic β-cell function. Next, we introduced HNF1a-Q125ter and HNF1a shRNA plasmids into the Ins-1 cell line and elucidated the molecular mechanism. hnf1a+/- zebrafish significantly decreased the β-cell number, insulin expression, and secretion. Moreover, β cells in hnf1a+/- dilated ER lumen and increased the levels of ER stress markers. Similar ER-stress phenomena were observed in an HNF1a-Q125ter-transfected Ins-1 cell. Follow-up investigations demonstrated that HNF1a-Q125ter induced ER stress through activating the PERK/eIF2a/ATF4 signaling pathway. Our study found a novel loss-of-function HNF1a-Q125ter variant which induced β-cell dysfunction by activating ER stress via the PERK/eIF2a/ATF4 signaling pathway.

Hypertriglyceridemia as a main feature associated with 17q12 deletion syndrome-related hepatocyte nuclear factor 1β-maturity-onset diabetes of the young.

SummaryHepatocyte nuclear factor 1β (HNF1B) gene is located on chromosome 17q12. It is a transcription factor implicated in the early embryonic development of multiple organs. HNF1B-associated disease is a multi-system disorder with variable clinical phenotypes. There are increasing reports suggesting that the 17q12 deletion syndrome should be suspected in patients with maturity-onset diabetes of the young type 5 (MODY5) due to the deletion of HNF1B gene. In contrast to classical 17q12 syndrome in childhood with neurological disorders and autism, patients with HNF1B-MODY deletion rarely had neuropsychological disorders or learning disabilities. The diagnosis of 17q12 deletion syndrome highlighted the phenotypic heterogeneity of HNF1B-MODY patients. In this study, we report the clinical course of a Thai woman with young-onset diabetes mellitus and hypertriglyceridemia as a predominant feature due to HNF1B deletion as part of the 17q12 deletion syndrome. Our findings and others suggest that hypertriglyceridemia should be considered a syndromic feature of HNF1B-MODY. Our case also highlights the need to use sequencing with dosage analyses to detect point mutations and copy number variations to avoid missing a whole deletion of HNF1B.Learning pointsMaturity-onset diabetes of the young type 5 (MODY5) may be caused by heterozygous point mutations or whole gene deletion of HNF1B. Recent studies revealed that complete deletion of the HNF1B gene may be part of the 17q12 deletion syndrome with multi-system involvement.The length of the deletion can contribute to the phenotypic variability in patients with HNF1B-MODY due to whole gene deletion.Using next-generation sequencing alone to diagnose MODY could miss a whole gene deletion or copy number variations. Specialized detection methods such as microarray analysis or low-pass whole genome sequencing are required to accurately diagnose HNF1B-MODY as a component of the 17q12 deletion syndrome.Molecular diagnosis is necessary to distinguish other acquired cystic kidney diseases in patients with type 2 diabetes which could phenocopy HNF1B-MODY.Hypertriglyceridemia is a possible metabolic feature in patients with HNF1B-MODY due to 17q12 deletion syndrome.

UDP-Glucose: A Cereblon-Dependent Glucokinase Protein Degrader.

We previously reported that glucokinase is ubiquitinated and degraded by cereblon with an unknown endogenous glucokinase protein degrader. Here, we show that UDP-glucose is a glucokinase protein degrader. We identified that both glucose and UDP-glucose bind to glucokinase and that both uridine and UDP-glucose bind to cereblon in a similar way to thalidomide. From these results, UDP-glucose was identified as a molecular glue between cereblon and glucokinase. Glucokinase produces glucose-6-phosphate in the pancreas and liver. Especially in β-cells, glucokinase is the main target of glucose for glucose-induced insulin secretion. UDP-glucose administration ubiquitinated and degraded glucokinase, lowered glucose-6-phosphate production, and then reduced insulin secretion in β-cell lines and mice. Maturity-onset diabetes of the young type 2 (MODY2) glucokinaseE256K mutant protein was resistant to UDP-glucose induced ubiquitination and degradation. Taken together, glucokinase ubiquitination and degradation signaling might be impaired in MODY2 patients.

182-OR: Clinical Effects of SGLT2 Inhibitors in HNF1A-Diabetes (MODY3) : A Case Series

Mutations in hepatocyte nuclear factor 1-alpha (HNF1A) cause HNF1A-diabetes (or maturity-onset diabetes of the young type 3 (MODY3)) . Treatment of HNF1A-diabetes is primarily based on sulphonylureas (SU) and secondarily insulins, glucagon-like peptide 1 receptor agonists (GLP1-RA) and dipeptidyl peptidase-4 inhibitors (DPP4i) . Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective glucose-lowering agents, cause body weight loss and protect from chronic kidney disease, heart failure and major adverse cardiovascular events. The utility of SGLT2i in patients with HNF1A-diabetes is unknown. Here, we describe a case series of five patients with HNF1A-diabetes treated with SGLT2i. Patient characteristics (median [range]) : age: 52 [35; 68] years; men/women: n=4/1; diabetes duration: 23 [9; 55] years; age at diabetes onset: 18 [13; 44] years; HbA1c: 6.9 [6.0; 7.4]% (52 [42; 57] mmol/mol) ; body weight: 92.3 [65.5; 95.1] kg; BMI: 25.6 [23.8; 29.4] kg/m2. At baseline, patients were treated with SU (n=5) , insulin (n=3; total daily dose: 15 [6; 25] IE divided into 1-4 injections/day) , DPP-4i (n=3) , GLP1-RA (n=2) , metformin (n=1) . All patients were started on empagliflozin mg QD. Follow-up was 1.5 [0.7; 1.8] years (total 6.2 patient years) . After three to six months of SGLT2i therapy, HbA1c was 6.1 [5.5; 7.5]% (43 [37; 59] mmol/mol) and had decreased in four patients (HbA1c change: -0.5 [-1.3; 0.7]% (-5 [-14; 8] mmol/mol)) , while body weight had decreased in all patients (change: -3.4 [-5.9; -1.5] kg) . During SGLT2i treatment, insulin was fully ceased in two patients and insulin dose was reduced from 15 IE/day to 3 IE/day in one patient. No serious adverse events were reported. Our data suggest that SGLT2i is safe, have glucose-lowering effects and is well-tolerated in HNF1A-diabetes, but randomized controlled trials are needed. Disclosure H.Maagensen: None. S.Haedersdal: None. J.Krogh: None. T.Hansen: None. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd.

Maturity-onset diabetes of the young type 3 and premature ovarian insufficiency: chance or causality: a case report and literature review.

SummaryWe present the case of a 23-year-old patient with maturity-onset diabetes of the young type 3 (MODY 3) and premature ovarian insufficiency (POI). There is no known correlation between MODY 3 and POI, although POI can impair glucose metabolism, and MODY can cause microvascular complications such as POI. We did not find literature describing a correlation between these two pathologies nor did we find similar cases described in the literature.Learning pointsMaturity-onset diabetes of the young type 3 (MODY 3) is an infrequent cause of diabetes that should be considered in young patients with atypical presentation of type 1 or type 2 diabetes.MODY 3 can be associated with microvascular complications of diabetes, which is why it is important to diagnose as early as possible.Impairment of glucose metabolism has been demonstrated in patients with premature ovarian insufficiency and menopause.

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus.

Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic β cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.

A rare, likely pathogenic GCK variant related to maturity-onset diabetes of the young type 2: A case report

A rare, likely pathogenic GCK variant related to maturity-onset diabetes of the young type 2: A case report

Current Perspectives in MODY Management—A Narrative Review

Maturity-onset diabetes of the young (MODY) is associated with familially inherited monogenic diabetes. It is characterized by genetic mutations leading to pancreatic β-cell dysfunction and subsequent insulin production. Clinical features of MODY include young-onset hyperglycemia associated with a lack of beta cell autoimmunity or insulin resistance. Glucose-lowering agents are the main therapeutic options for MODY. In this review, we have outlined the particular aspects of the most common types of MODY in order to assist clinical practitioners in this field.

Glycemic control in children and young adults with different types of diabetes mellitus in Ukraine

Introduction. Until recently, glycated hemoglobin (HbA1c) has not been studied in children with different types of diabetes mellitus (DM). With the development of molecular genetics, new types of diabetes have been diagnosed, including neonatal (ND) and maturity onset diabetes of the young (MODY), which usually require specific pathogenetic therapy, including sulfonylureas (SU), which improve glycemic control in patients with certain mutations. The aim of this study, which was conducted for the first time in Ukraine, was to analyze glycemic control in patients with different types of DM, including ND and MODY and changing their treatment after genetic testing. Materials and methods. We studied conducted the analysis of glycemic control in patients depending on the type of diabetes, namely: type 1 diabetes (n = 9282), type 2 diabetes (n = 23), ND (n = 16) with mutations KCNJ11, ABCC8 and MODY (n = 16) with mutations in HNF1A/HNF4A and ABCC8 genes. To confirm the nature of monogenic diabetes, targeting next-generation sequencing (tNGS) of all known neonatal and monogenic diabetes genes was performed. Results. According to the Register in 2018, in Ukraine the average age of children with type 1 DM was 11.5 ± 1.4 years, and the level of HbA1c was unsatisfactory (8.8 ± 2.01 %). The proportion of children who had ideal or optimal glycemic control (HbA1c

The use of SGLT2 inhibitors in achieving glycaemic control in maturity-onset diabetes of the young type 3.

SummaryMaturity-onset diabetes of the young type 3 (MODY3) accounts for approximately 50% of cases of MODY. First-line treatment with sulfonylureas has been well established for individuals with MODY3. In contrast, the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors in the treatment of individuals with MODY3 remains unclear. This case illustrates the in vivo effect of an SGLT2 inhibitor in a 30-year-old woman with MODY3 with poor glycaemic control despite the treatment with supramaximal doses of sulfonylurea and metformin. The addition of a SGLT2 inhibitor resulted in a rapid improvement in glycaemic control without any hypoglycaemic episodes. This case suggests that SGLT2 inhibitors may be an effective and potent treatment option in addition to sulfonylureas for individuals with MODY3.Learning pointsMaturity-onset diabetes of the young type 3 (MODY3) arises from mutations in the hepatocyte nuclear factor-1alpha gene, which controls the expression of sodium-glucose co-transporter 2 (SGLT2) in the kidneys.Paradoxically, despite individuals with MODY3 having reduced expression of SGLT2, SGLT2 inhibitors induce higher glycosuria in individuals with MODY3 compared to individuals with type 2 diabetes mellitus.SGLT2 inhibitors may be an effective treatment for achieving glycaemic control in individuals with MODY3.

Genetic analysis of a juvenile with maturity-onset diabetes of the young type 12

To explore the genetic basis for a juvenile with maturity-onset diabetes of the young type 12(MODY12). High-throughput sequencing was carried out to screen for the variants. Candidate variant was verified by Sanger sequencing. Pathogenity of the variant was predicted by searching the genetic databases and analysis by using bioinformatic software. Genetic testing indicated that the patient and his mother have both carried a heterozygous c.3976G>A variant (p.Glu1326Lys) in exon 32 of the ABCC8 gene. Prediction of the protein structure suggested the variant to be deleterious. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be uncertain significance. Whether the c.3976G>A variant of the ABCC8 gene is the cause of the disease in this patient or not depends on the functional studies and more case data. Above finding has enriched the spectrum of ABCC8 gene variants.

KLF11 Protects against Venous Thrombosis via Suppressing Tissue Factor Expression.

Krüppel-like factors (KLFs) play essential roles in multiple biological functions, including maintaining vascular homeostasis. KLF11, a causative gene for maturity-onset diabetes of the young type 7, inhibits endothelial activation and protects against stroke. However, the role of KLF11 in venous thrombosis remains to be explored. Utilizing stasis-induced murine deep vein thrombosis (DVT) model and cultured endothelial cells (ECs), we identified an increase of KLF11 expression under prothrombotic conditions both in vivo and in vitro. The expression change of thrombosis-related genes was determined by utilizing gain- and loss-of-function approaches to alter KLF11 expression in ECs. Among these genes, KLF11 significantly downregulated tumor necrosis factor-α (TNF-α)-induced tissue factor (TF) gene transcription. Using reporter gene assay, chromatin immunoprecipitation assay, and co-immunoprecipitation, we revealed that KLF11 could reduce TNF-α-induced binding of early growth response 1 (EGR1) to TF gene promoter in ECs. In addition, we demonstrated that conventional Klf11 knockout mice were more susceptible to developing stasis-induced DVT. These results suggest that under prothrombotic conditions, KLF11 downregulates TF gene transcription via inhibition of EGR1 in ECs. In conclusion, KLF11 protects against venous thrombosis, constituting a potential molecular target for treating thrombosis.

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

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