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

Diabetologia 2026 Open access

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Authors: Thomas W. Laver, Aparajita Sriram, Matthew N. Wakeling, Zeynep Şıklar, Farah Kobaisi, Oğuzhan Kalyon, Andrew T. Hattersley, Michael N. Weedon, Sarah E. Flanagan, Elisa De Franco, Kevin Colclough, Kashyap A. Patel
DOI: 10.1007/s00125-026-06685-7
Cited by: 2
References: 37

Abstract

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 nonsense-mediated decay (NMD). We aimed to systematically evaluate the pathogenicity of LOF variants, stratified by NMD-triggering and NMD-escape status, across all known MODY genes. METHODS: We analysed ultra-rare LOF variants (minor allele frequency

Fields of Study & Subjects

Genomics and Rare Diseases Hereditary Neurological Disorders Neurogenetic and Muscular Disorders Research

Publication details

Journal / source
Diabetologia
Publisher
Springer Science and Business Media LLC
Volume
69
Issue
6
Pages
1569–1580
Publication date
3 March 2026
Language
EN