scholarly journals Application of NGS to improve the effectiveness of molecular genetic diagnostics of monogenic forms of diabetes in children

2020 ◽  
pp. 86-88
Author(s):  
О.С. Глотов ◽  
Е.А. Серебрякова ◽  
М.Е. Туркунова ◽  
Е.Б. Башнина ◽  
А.С. Глотов ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Variants ◽  
Wide Spectrum ◽  
Direct Sequencing ◽  
Monogenic Diabetes ◽  
Genetic Diagnostics ◽  
Number Of Patients

Исследованы образцы ДНК 60 пациентов с подозрением на наличие моногенного сахарного диабета (МСД-MODY) путем секвенирования NGS панели 13 генов MODY и 22 гена «неонатального» диабета и синдромальных форм диабета. МСД был подтвержден у 55% (n=33). Из 33 пациентов 27 (81,8%) имели мутации (варианты) в MODY генах. Наиболее часто встречались варианты в гене GCK-31,6% (n=19). Спектр вариантов в гене GCK включал 13 миссенс мутаций, 3 нонсенс, 4 со сдвигом рамки считывания и 1 в промоторной области. Были также выявлены варианты в других генах: HNF1A (n=3), WFS1(n=4), PAX4 (n=1), EIF2AK3 (n=1, гомозигота), GATA6 (n=1), KCNJ11(n=1), ABCC8 (n=1), SLC19A2 (n=2), BLK (n=2). Из 38 детектированных вариантов 15 оказались новыми. Высокая выявляемость может быть связана как с особенностями нашей группы, так и с использованным биоинформатическим подходом. Молекулярно-генетическая верификация диагноза при помощи NGS секвенирования позволяет повысить эффективность диагностики, прогнозировать течение заболевания и вносить коррективы в лечение СД. The present study included 60 unrelated Russian children with non-type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were analyzed using whole-exome sequencing (WES) in a panel of 35 genes causative of maturity onset diabetes of the young (MODY) and transient or permanent neonatal diabetes. Verification of the WES results was performed using PCR-direct sequencing. A total of 38 genetic variants were identified in 33 out of 60 patients (55%). The majority of patients (27/33, 81.8%) had variants in MODY-related genes: GCK (n=19), HNF1A (n=2), PAX4 (n=1), ABCC8 (n=1), KCNJ11 (n=1), GCK+HNF1A (n=1), GCK+BLK (n=1) and GCK+BLK+WFS1 (n=1). A total of 6 patients (6/33, 18.2%) had variants in MODY-unrelated genes: GATA6 (n=1), WFS1 (n=3), EIF2AK3 (n=1) and SLC19A2 (n=1). A total of 15 out of 38 variants were novel, including GCK, HNF1A, BLK, WFS1, EIF2AK3 and SLC19A2. To summarize, the present study demonstrates a high frequency and a wide spectrum of genetic variants causative of monogenic diabetes in Russian children with non-type 1 diabetes mellitus. The spectrum includes previously known and novel variants in MODY-related and unrelated genes, with multiple variants in a number of patients. The prevalence of GCK variants indicates that diagnostics of monogenic diabetes in Russian children may begin with testing for MODY2. However, the remaining variants are present at low frequencies in 9 different genes, altogether amounting to ~50% of the cases and highlighting the efficiency of using WES in non-GCK-MODY cases.

scholarly journals Type 1 Diabetes Mellitus-Associated Genetic Variants Contribute to Overlapping Immune Regulatory Networks

2018 ◽  
Vol 9 ◽  
Author(s):  
Denis M. Nyaga ◽  
Mark H. Vickers ◽  
Craig Jefferies ◽  
Jo K. Perry ◽  
Justin M. O’Sullivan
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Variants ◽  
Regulatory Networks

Changes in the presentation of newly diagnosed type 1 diabetes in children during the COVID-19 pandemic in a tertiary center in Southern Turkey

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Semine Özdemir Dilek ◽  
Fatih Gürbüz ◽  
İhsan Turan ◽  
Can Celiloğlu ◽  
Bilgin Yüksel
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Islet Cell Antibodies ◽  
Acid Decarboxylase ◽  
High Morbidity ◽  
Newly Diagnosed ◽  
Number Of Patients ◽  
Tertiary Center

Abstract Objectives The COVID-19 pandemic is a global health problem with high morbidity and mortality. This study aimed to investigate patients who were diagnosed with type 1 diabetes during the pandemic and evaluate the effect of the pandemic on the clinical findings of these patients by comparing them with findings from a year prior. Methods Patients diagnosed with type 1 diabetes mellitus between 2019 and 2021 were separated into two groups: Patients diagnosed prepandemic and those diagnosed during the pandemic. Results The number of newly diagnosed diabetes cases increased from 46 in the prepandemic period to 74 in the pandemic period. The number of cases diagnosed with diabetic ketoacidosis (DKA) in the clinic increased from 58.7 to 91.9%. We found that moderate and severe DKA rates from 18.5 and 14.8% to 23.5 and 22.1%, respectively. Besides, the average HbA1c was higher, while the average bicarbonate was lower in cases diagnosed during the pandemic period compared to the prepandemic period (p=0.048 and p<0.001, respectively). We found that celiac autoantibody positivity antibodies to glutamic acid decarboxylase (anti GAD) positivity, and islet cell antibodies (ICA), ICA and anti GAD positivity coexistence were higher (p=0.045, p=0.008, and p=0.007, respectively) among the patients diagnosed during the pandemic. Conclusions We observed an increase in the number of patients newly diagnosed with type 1 diabetes mellitus, an increase in autoantibody positivity, and higher rates and severity of DKA during the COVID-19 pandemic period compared to the prepandemic period.

Functional relevance for type 1 diabetes mellitus-associated genetic variants by using integrative analyses

2015 ◽  
Vol 76 (10) ◽  
pp. 753-758 ◽  
Author(s):  
Ying-Hua Qiu ◽  
Fei-Yan Deng ◽  
Zai-Xiang Tang ◽  
Zhen-Huan Jiang ◽  
Shu-Feng Lei
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Variants ◽  
Integrative Analyses ◽  
Functional Relevance

scholarly journals Coeliac screening in a Scottish cohort of children with type 1 diabetes mellitus: is DQ typing the way forward?

2015 ◽  
Vol 101 (3) ◽  
pp. 230-233 ◽  
Author(s):  
R T Mitchell ◽  
A Sun ◽  
A Mayo ◽  
M Forgan ◽  
A Comrie ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Additional Cost ◽  
Hla Typing ◽  
Hla Genotypes ◽  
Number Of Patients ◽  
Increased Risk ◽  
Hla Dq2

BackgroundChildren with type 1 diabetes mellitus (T1DM) are at increased risk of coeliac disease (CD). Recent guidelines indicate coeliac screening should include HLA typing for CD predisposing (DQ2/DQ8) alleles and those negative for these alleles require no further coeliac screening.MethodsChildren (n=176) with T1DM attending clinics across two Scottish regions were screened for HLA DQ2/DQ8 as part of routine screening. Data collected included the frequency of DQ2/DQ8 genotypes and the additional cost of HLA screening.ResultsOverall, DQ2/DQ8 alleles were identified in 94% of patients. The additional cost of HLA typing was £3699.52 (£21.02 per patient). All patients with known CD (11/176) were positive for DQ2/DQ8 and all were diagnosed with CD within 5 years of T1DM diagnosis.ConclusionsThe vast majority of children with T1DM have CD-predisposing HLA genotypes limiting the number of patients that can be excluded from further screening. We conclude that HLA genotyping is not currently indicated for CD screening in this population.

scholarly journals MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus

2019 ◽  
Vol 60 (12) ◽  
pp. 3937 ◽  
Author(s):  
Ebony Liu ◽  
Georgia Kaidonis ◽  
Bennet J. McComish ◽  
Mark C. Gillies ◽  
Sotoodeh Abhary ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Variants

Monogenic diabetes and type 1 diabetes mellitus: a challenging combination

2014 ◽  
Vol 31 (8) ◽  
pp. 327-330 ◽  
Author(s):  
Suma Uday ◽  
Fiona M Campbell ◽  
Julie Cropper ◽  
Maggie Shepherd
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Monogenic Diabetes

scholarly journals Association of Genetic Variants at 3q22 with Nephropathy in Patients with Type 1 Diabetes Mellitus

2009 ◽  
Vol 84 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Bing He ◽  
Anne-May Österholm ◽  
Anna Hoverfält ◽  
Carol Forsblom ◽  
Eyrún Edda Hjörleifsdóttir ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Variants

scholarly journals Late-onset type 1 diabetes mellitus or latent autoimmune diabetes in adults: a teachable moment

2020 ◽  
Author(s):  
Isabel Borges ◽  
Roberto Añez ◽  
Mervin Chavez-Castillo ◽  
Juan Salazar
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Late Onset ◽  
Autoimmune Diabetes ◽  
Wide Spectrum ◽  
Clinical Form ◽  
Latent Autoimmune Diabetes

Adult-onset autoimmune diabetes (AOAD) is clinical form of diabetes with a wide spectrum of genotypical and phenotypical manifestations, which has risen in prominence in recent decades, probably due to greater interest in its pathogenic mechanisms, and increased identification of autoimmune markers. The clinical presentation may vary from type 1 diabetes mellitus to latent autoimmune diabetes in adults, which although clearly distinct from a theoretical viewpoint, may pose various clinical pitfalls in practice. We present the case of a patient with AOAD which featured several diagnostic challenges during follow-up.

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