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

ABSTRACT: An accurate genetic diagnosis of maturity-onset diabetes of the young (MODY) is critical for personalized treatment. To avoid misdiagnosis, only genes with strong evidence of causality must be tested. Heterozygous variants in NEUROD1, PDX1, APPL1, and WFS1 have been implicated in MODY, but strong genetic evidence supporting causality is lacking. We therefore assessed their existing genetic evidence and performed gene-level burden tests in a large MODY cohort, alongside two established MODY genes as positive controls (HNF1A-high penetrance, RFX6-low penetrance). The first reported MODY-associated variants in NEUROD1, PDX1, APPL1, and WFS1 were <1:20,000 frequency. Based on the small number of large published pedigrees per gene (n < 3), MODY-associated variants showed only modest cosegregati

SUBMITTER: Sriram A 

PROVIDER: S-EPMC7617998 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature