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

2021 ◽  
Vol 12 ◽  
Author(s):  
Juyi Li ◽  
Meng Shu ◽  
Xiufang Wang ◽  
Aiping Deng ◽  
Chong Wen ◽  
...  
Keyword(s):  
Treatment Plan ◽  
Compliance Rate ◽  
Family Members ◽  
Asian Population ◽  
Chinese Family ◽  
Maturity Onset Diabetes ◽  
Good Glycemic Control ◽  
Family History Of Diabetes ◽  
Onset Diabetes ◽  
Pathogenic Gene

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

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Chaoyan Tang ◽  
Liheng Meng ◽  
Ping Zhang ◽  
Xinghuan Liang ◽  
Chaozhi Dang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Fasting Blood Glucose ◽  
Family Members ◽  
Missense Variant ◽  
Postprandial Blood Glucose ◽  
Chinese Family ◽  
Oral Glucose ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

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.

Transient neonatal diabetes due to a disease causing novel variant in the ATP-binding cassette subfamily C member 8 (ABCC8) gene unmasks maturity-onset diabetes of the young (MODY) diabetes cases within a family

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Eleni Z Giannopoulou ◽  
Olga Ovcarov ◽  
Elisa De Franco ◽  
Fabian Kassberger ◽  
Susanne Nusser ◽  
...  
Keyword(s):  
Autoimmune Diabetes ◽  
Family Members ◽  
Neonatal Diabetes ◽  
Atp Binding ◽  
Adult Onset ◽  
Family History Of Diabetes ◽  
Abcc8 Gene ◽  
Onset Diabetes ◽  
Novel Variant ◽  
Atp Binding Cassette

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare monogenic diabetes form, occurring mainly from ATP-binding cassette subfamily C member 8 (ABCC8) and KCNJ11 mutations. ABCC8 mutations have also been found to cause adult-onset diabetes. What is new?: •Novel ABCC8 mutation in an NDM case •Heterogeneous clinical presentation of diabetes and response to sulfonylurea therapy among family members with the same ABCC8 mutation.Case presentationWe report the case of a newborn with NDM and a heterozygous ABCC8 novel variant (c.3835G>A), successfully treated with sulfonylurea. The same ABCC8 variant was found in two other family members, already treated for type 2 diabetes.ConclusionsThis case demonstrates the variable phenotypic presentation of diabetes due to a novel ABCC8 mutation (c.3835G>A), ranging from transient NDM to adult-onset, insulin-demanding diabetes, among family members. Genetic testing in young individuals with a strong family history of diabetes, presenting with non-autoimmune diabetes is recommended as it can determine prognosis and treatment of affected family members.

MODY in Ukraine: genes, clinical phenotypes and treatment

2017 ◽  
Vol 30 (10) ◽  
Author(s):  
Evgenia Globa ◽  
Nataliya Zelinska ◽  
Lenka Elblova ◽  
Petra Dusatkova ◽  
Ondrej Cinek ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family Members ◽  
Genetic Diagnosis ◽  
Maturity Onset Diabetes ◽  
Genetic Etiology ◽  
Clinical Phenotypes ◽  
Onset Diabetes ◽  
Patients With Diabetes ◽  
Made In

AbstractBackground:Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members.Methods:Genetic testing of the most prevalent MODY genes (Results:A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%).Conclusions:Genetic testing identified pathogenic

A genetic diagnosis of maturity-onset diabetes of the young (MODY): experiences of patients and family members

2015 ◽  
Vol 32 (10) ◽  
pp. 1385-1392 ◽  
Author(s):  
A. R. Bosma ◽  
T. Rigter ◽  
S. S. Weinreich ◽  
M. C. Cornel ◽  
L. Henneman
Keyword(s):  
Family Members ◽  
Genetic Diagnosis ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

scholarly journals NEUROD1 Mutation in an Italian Patient With Maturity Onset Diabetes of the Young 6: a Case Report

2021 ◽  
Author(s):  
Lucia Brodosi ◽  
Bianca Baracco ◽  
Vilma Mantovani ◽  
Loris Pironi
Keyword(s):  
Case Report ◽  
Beta Cells ◽  
Early Onset ◽  
Genetic Mutation ◽  
Maturity Onset Diabetes ◽  
Family History Of Diabetes ◽  
Onset Diabetes ◽  
Dominant Disease ◽  
Recent Case Report ◽  
Single Genetic Mutation

Abstract Background and Aims: maturity onset diabetes of the young (MODY) is a monogenic, autosomal, dominant disease characterized by a single genetic mutation that results in beta-cells disfunction with consequent hyperglycemia. It represents a rare form of diabetes (1-2% of all the cases). Sulphonylureas (SU) represent the first line treatment for this form of diabetic disease. NEUROD1 is a transcription factor expressed by pancreatic and nervous tissues that is necessary for a proper development of beta cells. A mutation of NEUROD1 gene has been found to cause beta-cells dysfunction, inadequate insulin secretion, and hyperglycemia (MODY 6). A recent case report has documented for the first time a new missense mutation (p.Met114Leu c.340A> C), of the NEUROD1 gene pathogenetic for diabetes mellitus.Methods and Results: We report the case of a 50 years-old man who presented the same mutation, and who was able to suspend rapid insulin after the diagnosis and treatment with SU. Interestingly, our patient had an early onset dilated cardiomyopathy but no other data about cardiac diseases in patients with MODY 6 are available.Conclusions: Diagnostic criteria for MODY can overlap with other kinds of diabetes and most cases are still misdiagnosed as diabetes type 1 or 2. The disease should be suspected in patients with a strong family history of diabetes, normal BMI, early onset and no autoimmunity.

Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes

2019 ◽  
Vol 32 (7) ◽  
pp. 759-765 ◽  
Author(s):  
Zhu Ming-Qiang ◽  
Dai Yang-Li ◽  
Huang Ke ◽  
Wu Wei ◽  
Fu Jun-Fen ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Disease Diagnosis ◽  
Tolerance Test ◽  
Chinese Children ◽  
Chinese Patients ◽  
Molecular Characteristics ◽  
Oral Glucose ◽  
Maturity Onset Diabetes ◽  
Family History Of Diabetes ◽  
Onset Diabetes

Abstract Background To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY). Methods A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing. Results There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4–15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55–4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK-MODY had lower glycated hemoglobin (HbA1c) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK-MODY was identified by incidental hyperglycemia without glycosuria. GCK-MODY without drug management and hepatocyte nuclear factor-1 alpha (HNF4A) or HNF1A-MODY with sulfonylurea therapy obtained good glucose controlling. Conclusions Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4. The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

scholarly journals Maturity-onset diabetes of the young type 5 a MULTISYSTEMIC disease: a CASE report of a novel mutation in the HNF1B gene and literature review

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Juan Camilo Mateus ◽  
Carolina Rivera ◽  
Miguel O’Meara ◽  
Alex Valenzuela ◽  
Fernando Lizcano
Keyword(s):  
Diabetes Mellitus ◽  
Novel Mutation ◽  
Maturity Onset Diabetes ◽  
Family History Of Diabetes ◽  
Multiple Organs ◽  
Onset Diabetes ◽  
Multisystem Involvement ◽  
Multisystemic Disease ◽  
History Of ◽  
And Function

Abstract Background Diabetes mellitus with autosomal dominant inheritance, such as maturity-onset diabetes of the young (MODY), is a genetic form of diabetes mellitus. MODY is a type of monogenic diabetes mellitus in which multiple genetic variants may cause an alteration to the functioning of beta cells. The three most known forms of MODY are caused by modifications to the hnf4a, gck, and hnf1a genes. However, other MODY variants can cause multiple alterations in the embryonic development of the endoderm. This is the case in patients presenting with MODY5, who have a mutation of the hepatic nuclear factor 1B (hnf1b) gene. Case presentation We present the clinical case of a 15 year-old patient with a family history of diabetes mellitus and a classical MODY type 5 (MODY5) phenotype involving the pancreas and kidney, with a novel, unreported mutation in the hnf1b gene. Conclusions MODY5 is characterised by a mutation in the hnf1b gene, which plays an important role in the development and function of multiple organs. It should be suspected in patients with unusual diabetes and multisystem involvement unrelated to diabetes. Graphical abstract

Sign in / Sign up

Export Citation Format

Share Document