Novel PAX4 variant in a child and family with diabetes mellitus - case report and review of the literature

• Main Authors: Lee, Yee-Lin, Ting, Tzer-Hwu, Lim, Chong-Teik, Arrumugam, Crystal Arthini, Karuppiah, Thilakavathy, Ling, King-Hwa
• Format: Article
• Published: Walter de Gruyter GmbH 2023
• Online Access: http://psasir.upm.edu.my/id/eprint/110050/; https://www.degruyter.com/document/doi/10.1515/jpem-2023-0171/html
• Institution: Universiti Putra Malaysia

Objectives: PAX4 (Paired box 4), a transcription factor crucial in pancreatic beta cell development and function, is a rare cause of maturity-onset diabetes of the young (MODY). What is new? A novel PAX4 variant is verified by family segregation study to be likely pathogenic. A child below 10 years of age diagnosed to have PAX4-MODY, differing from previously reported paediatric cases diagnosed in adolescence. Case presentation: A child with diabetes diagnosed at age 8 years, harbored a PAX4 variant, c.890G>A (p.Gly297Asp), initially classified as variant of uncertain significance. Eleven family members (7 adults and 4 children) with and without diabetes across 3 generations were genotyped. The variant co-segregated with diabetes or prediabetes across 3 generations of the family. The variant is reclassified as likely pathogenic according to standard guidelines. Conclusion: Genetic testing is essential to confirm PAX4-- MODY as the presentation is variable even within the same family. PAX4 mutation needs to be considered in MODY genetic testing in Asian patients.