Rare Variants in <i>NEUROD1</i> and <i>PDX1</i> Are Low-Penetrance Causes of MODY, Whereas Those in <i>APPL1</i> and <i>WFS1</i> Are Not Associated With MODY
Testing genes with limited evidence of causality risks misdiagnosis of maturity-onset diabetes of the young (MODY). There is limited evidence as to whether rare variants in PDX1, NEUROD1, APPL1, and WFS1 cause MODY. Rare damaging variants in APPL1 and WFS1 are not enriched in a MODY cohort, but those in PDX1 and NEUROD1 are, at a level similar to low-penetrance MODY genes. PDX1 and NEUROD1 should be included in MODY gene panels, while heterozygous APPL1 and WFS1 variants should not be reported as causes of MODY.
Authors
- Kevin Colclough (ORCID: https://orcid.org/0000-0003-0566-4853)
- Matthew N. Wakeling (ORCID: https://orcid.org/0000-0002-6542-9241)
- Thomas W. Laver (ORCID: https://orcid.org/0000-0001-6399-0089)
- Andrew Tym Hattersley (ORCID: https://orcid.org/0000-0001-5620-473X)
- Kashyap Patel (ORCID: https://orcid.org/0000-0002-9240-8104)
- Michael N. Weedon (ORCID: https://orcid.org/0000-0002-6174-6135)
- Aparajita Sriram
Institutions
- University of Exeter (GB)
- Royal Devon & Exeter NHS Foundation Trust (GB)
Publication Details
- Journal
- Diabetes
- Published
- 2025-08-08
- DOI
- https://doi.org/10.2337/db25-0442
- Citations
- 5
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- Wellcome Trust
- European Foundation for the Study of Diabetes