OBJECTIVE. To evaluate the clinical utility of incorporating a type 1 diabetes genetic risk score (T1DGRS) into monogenic diabetes gene panel testing for i

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

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...

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...

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...

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...

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

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

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...

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 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.

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.

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

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 ...