MODY probability calculator for GCK and HNF1A screening in a multiethnic background population

Tarantino, Roberta Magalhães; Abreu, Gabriella de Medeiros; Fonseca, Ana Carolina Proença de; Kupfer, Rosane; Pereira, Maria de Fátima Carvalho; Júnior, Mário Campos; Zajdenverg, Lenita; Rodacki, Melanie

doi:10.20945/2359-3997000000173

Cited by 8 publications

(11 citation statements)

References 26 publications

(29 reference statements)

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“…In particular, MPC performed better within GCK ‐MODY individuals than within HNF1A ‐MODY (Figures 3‐4). We might argue that this may result both from the high frequency (41%) of GCK ‐MODY probands included in the MODY clinical prediction model development and the relatively ‘homogeneous’ clinical presentation that characterizes this MODY‐subtype, in contrast with HNF1A ‐MODY clinical heterogeneity 10–25 …”

Section: Discussionmentioning

confidence: 99%

“…We might argue that this may result both from the high frequency (41%) of GCK-MODY probands included in the MODY clinical prediction model development and the relatively 'homogeneous' clinical presentation that characterizes this MODY-subtype, in contrast with HNF1A-MODY clinical heterogeneity. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Our work proposes that a higher post-test probability score (>36%) using MPC does yield a high mutation detection rate in our population. On the other hand, applying strict criteria such as ours is likely to miss a proportion of affected individuals, although significantly less than when using clinical features alone.…”

Section: % Will Have Mody (Ppv) This Mpc Prediction Model By Shields ...mentioning

confidence: 91%

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MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance

Santos

Fonseca

Monteiro

et al. 2022

Endocrino Diabet & Metabol

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Introduction MODY probability calculator (MPC) represents an easy‐to‐use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early‐onset monogenic diabetes. Methods This single‐centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort. Results Seventy‐three individuals were included according to inclusion criteria: 20 glucokinase (GCK‐MODY); 16 hepatocyte nuclear factor 1A (HNF1A‐MODY); 2 hepatocyte nuclear factor 4A (HNF4A‐MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes‐positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%–85%). In our cohort, the best cut‐off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively. Conclusions In a highly pre‐selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut‐off of 36%. Further geographical and population adjustments are warranted for general use.

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Section: Discussionmentioning

confidence: 99%

Section: % Will Have Mody (Ppv) This Mpc Prediction Model By Shields ...mentioning

confidence: 91%

MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance

Santos

Fonseca

Monteiro

et al. 2022

Endocrino Diabet & Metabol

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show abstract

“…In a study in which MPC was evaluated together with MODY genetic test results in a multiethnic population, MODY probability rate calculated by MPC was higher than 50% in patients with glucokinase gene mutation. Therefore 50% was taken as cutoff the possible diagnosis of MODY 12 .…”

Section: Discussionmentioning

confidence: 99%

MODY Probability Ratios in Patients Diagnosed with Type 2 Diabetes Mellitus at a Young Age

Keskinler¹,

Erbakan²,

Oğuz³

2020

MMJ

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Objective Maturity-onset diabetes of the young (MODY) is a non-rare group of monogenic inherited diabetes which is commonly confused with type 1 and type 2 diabetes. Due to high costs of genetic tests that provide a definitive diagnosis, some screening scales are used to identify the high-risk patients. In this study, we aimed to evaluate whether (MODY Probability Calculator [MPC]) which is one of the screening tests will be helpful in identifying our high-risk patients among young patients with type 2 diabetes Method The patients received the diagnosis of type 2 diabetes aged <35 years were included in the study. The anthropometric characteristics of the patients, the treatments they received at the time of diagnosis, and the current treatments were recorded by retrospectively scanning patient files.The patients with the diagnosis of type 1 diabetes having autoantibodies to the pancreas were excluded from the study. The probability of MODY was calculated using MPC.. Results The mean age of 72 patients (40% female) was 41.5±7.2 years. Eighteen of the patients (25%) were using insulin at the time of diagnosis. The mean HbA1c was 8.6±2.2% and C-peptide was 2.35±1.52 ng/ml. The mean MODY positive predictive score calculated by MPC for risk of MODY was 11.23 percent. There were 61 patients (84.7%) with a risk of ≤20%, 9 patients (12.5%) with a risk of 20-50%, and 2 patients (2.8%) with ≥50%. In the group with MODY PPV score >20%, the age of onset of diabetes and the body mass index was significantly lower than the others (p<0.05, for both). There was no significant difference between current treatments of both groups. Conclusion It has been reported that MODY risk calculated by MPC may yield different results in different populations. The results of this study showed that 15% of our young-onset diabetes patients had an MPC score above 20 percent. Requesting MODY genetic tests in this 15% of the patient group can be presented as a practical suggestion.

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“…Nineteen probands were enrolled in GCK screening and 16 were studied for HNF1A . In addition, twenty-one negative patients for HNF1A and one patient negative for GCK , previous reported by our group ( 8 ), were included for the screening of the other MODY genes. All negative patients for GCK variants were analyzed for HNF1A gene.…”

Section: Methodsmentioning

confidence: 99%

Identification of Variants Responsible for Monogenic Forms of Diabetes in Brazil

et al. 2022

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Monogenic forms of diabetes mellitus may affect a significant number of patients of this disease, and it is an important molecular cause to be investigated. However, studies of the genetic causes of monogenic diabetes, especially in populations with mixed ethnic backgrounds, such as the one in Brazil, are scarce. The aim of this study was to screen several genes associated with monogenic diabetes in fifty-seven Brazilian patients with recurrence of the disease in their families and thirty-four relatives. Inclusion criteria were: Age of onset ≤ 40 years old, BMI < 30 kg/m², at least two affected generations and negative anti-GAD and anti-IA2 antibodies. MODY genes HNF4A, GCK, HNF1A, HNF1B, NEUROD1, KLF11, PAX4, INS, KCNJ11, and MT-TL1 were sequenced by Sanger sequencing. We identified a total of 20 patients with variants, 13 GCK-MODY, four HNF1A-MODY, and one variant in each of the following genes, HNF4A, HNF1B and MT-TL1. Segregation analysis was performed in 13 families. Four variants were novel, two in GCK (p.(Met115Val) [c.343A>G] and p.(Asp365GlufsTer95) [c.1094_1095insGCGA]) and two in HNF1A (p.(Tyr163Ter) [c.489C>G] and p.(Val380CysfsTer39) [c.1136_1137insC]). Here we highlight the importance of screening for monogenic diabetes in admixed populations.

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MODY probability calculator for GCK and HNF1A screening in a multiethnic background population

Cited by 8 publications

References 26 publications

MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance

MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance

MODY Probability Ratios in Patients Diagnosed with Type 2 Diabetes Mellitus at a Young Age

Identification of Variants Responsible for Monogenic Forms of Diabetes in Brazil

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