Systematic analysis of loss-of-function variants across MODY genes demonstrates gene-specific effects and expands the spectrum of INS variants causing MODY
The pathogenicity of LOF variants in MODY genes depends on gene context and NMD status. Heterozygous NMD-escape LOF variants in INS are a novel cause of MODY. These findings provide systematic gene-level evidence to inform variant interpretation guidelines and improve the accuracy of MODY diagnosis in clinical practice.
Authors
- Kevin Colclough (ORCID: https://orcid.org/0000-0003-0566-4853)
- Thomas W. Laver (ORCID: https://orcid.org/0000-0001-6399-0089)
- Andrew Tym Hattersley (ORCID: https://orcid.org/0000-0001-5620-473X)
- Oğuzhan Kalyon
- Aparajita Sriram
- Elisa De Franco
- Kashyap A. Patel
- Farah Kobaisi
- Michael N. Weedon
- Matthew N. Wakeling
Institutions
- Centre National de la Recherche Scientifique (FR)
- Ankara University (TR)
- Inserm (FR)
- Université Paris Cité (FR)
- University of Exeter (GB)
- Royal Devon & Exeter NHS Foundation Trust (GB)
- Institut Cochin (FR)
Publication Details
- Journal
- Diabetologia
- Published
- 2026-03-03
- DOI
- https://doi.org/10.1007/s00125-026-06685-7
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- National Institute for Health and Care Research
- Medical Research Council