Low-level mosaic variants causing the pancreatic disease congenital hyperinsulinism can be detected from blood DNA

A substantial proportion of individuals with a well-defined monogenic disorder remain without a genetic diagnosis. Low-level mosaic pathogenic variant…

sciencedirect.com

Genotype-first approach reveals monogenic lipodystrophy is underdiagnosed, with health and mortality risks

Monogenic lipodystrophy is more common than currently recognised and most cases remain undiagnosed despite significant cardiometabolic and mortality risks. These findings highlight the value of genoty...

thelancet.com

Polygenic background contributes to GCK-MODY clinical presentation and glycaemic variability - Diabetologia

Aims/hypothesis GCK-MODY (glucokinase MODY) causes lifelong, mild hyperglycaemia with high penetrance. Variation in glycaemic phenotype among carriers remains unexplained. We hypothesised that polygen...

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Polygenic background contributes to GCK-MODY clinical presentation and glycaemic variability - Diabetologia

Aims/hypothesis GCK-MODY (glucokinase MODY) causes lifelong, mild hyperglycaemia with high penetrance. Variation in glycaemic phenotype among carriers remains unexplained. We hypothesised that polygen...

link.springer.com

Systematic analysis of loss-of-function variants across MODY genes demonstrates gene-specific effects and expands the spectrum of INS variants causing MODY - Diabetologia

Aims/hypothesis Accurate interpretation of loss-of-function (LOF) variants in MODY genes is essential for diagnosis but remains challenging, particularly for variants that are predicted to escape nons...

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MODY Is Prevalent in Later-Onset Diabetes and Has Potential for Targeted Therapy but Is Challenging to Identify

Maturity onset diabetes of the young (MODY) can present after the age of 40 years, but its prevalence and clinical characteristics, and the utility of simp

doi.org

Population prevalence, penetrance, and mortality for genetically confirmed MODY

AbstractContext. Diagnosing Maturity-Onset Diabetes of the Young (MODY) is clinically important for treatment and prognosis. However, phenotype-based studi

doi.org

The minor spliceosome is a master immune regulator

Pathogenic variants in non-coding genes are emerging as critical contributors to human rare diseases. We identified 19 individuals with early-onset diabetes (diagnosed <5 years) and additional clinica...

medrxiv.org

Common genetic variants modify disease risk and clinical presentation in monogenic diabetes - Nature Metabolism

In clinical and population-based cohorts, a strong contribution of polygenic risk for type 2 diabetes (T2D) significantly modifies the onset and phenotypic variability of maturity-onset diabetes of th...

nature.com

Polygenic determinants of monogenic diabetes

Nature Metabolism, Published online: 09 September 2025; doi:10.1038/s42255-025-01380-0In a new study, the polygenic background of type 2 diabetes (T2D) is found to determine the risk of diabetes associated with so-called monogenic forms of β-cell diabetes, as well as the age at onset and severity of diabetes.

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Common genetic variants modify disease risk and clinical presentation in monogenic diabetes

Nature Metabolism, Published online: 09 September 2025; doi:10.1038/s42255-025-01372-0In clinical and population-based cohorts, a strong contribution of polygenic risk for type 2 diabetes (T2D) significantly modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY). This polygenic T2D burden may also account for MODY-like individuals without identified monogenic causes.

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Rare Variants in NEUROD1 and PDX1 Are Low-Penetrance Causes of MODY, Whereas Those in APPL1 and WFS1 Are Not Associated With MODY

An accurate genetic diagnosis of maturity-onset diabetes of the young (MODY) is critical for personalized treatment. To avoid misdiagnosis, only genes with

diabetesjournals.org

Global perspectives on monogenic forms of diabetes - Diabetologia

Monogenic forms of diabetes represent an uncommon but very heterogeneous subset of the disease, with variable associated clinical features and key differences in treatment options. In this review, we ...

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