Complete loss of PAX4 causes transient neonatal diabetes in humans.

ABSTRACT:

Objective

Gene discovery studies in individuals with diabetes diagnosed within 6 months of life (neonatal diabetes, NDM) can provide unique insights into the development and function of human pancreatic beta-cells.

Methods

We performed genome sequencing in a cohort of 43 consanguineous individuals with NDM in whom all the known genetic causes had previously been excluded. We used quantitative PCR and RNA-sequencing in CRISPR-edited human induced pluripotent stem cells (iPSCs), and CUT&RUN-sequencing in EndoC-βH1 cells to investigate the effect of PAX4 loss on human pancreatic development.

Results

We describe the identification of homozygous PAX4 loss-of-function variants in 2 individuals with transient NDM: a p.(Arg126∗) stop-gain variant and a c.-352_104del deletion

SUBMITTER: Russ-Silsby J 

PROVIDER: S-EPMC12275979 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature