MNX1 – Permanent Neonatal Diabetes Mellitus

Homozygous MNX1 variants have been reported in two unrelated permanent neonatal diabetes mellitus (PNDM) probands, both harboring the same c.816C>A (p.Phe272Leu) change, identified via homozygosity mapping in a consanguineous family (one female) and in a second male presenting with severe diabetic ketoacidosis ([PMID:23562494]; [PMID:36586106]). In both cases, no additional affected relatives were described, consistent with an autosomal recessive inheritance pattern. Expression analysis in human embryonic pancreatic islet samples demonstrated significant enrichment of MNX1 in epithelium versus mesenchyme, suggesting a critical role in pancreatic β-cell development ([PMID:23562494]). No functional assays of the specific p.Phe272Leu mutant have been reported, and replication beyond these two cases is lacking. Overall, the current evidence supports a limited gene–disease association, warranting further genetic and mechanistic studies in diverse cohorts. Key take-home: MNX1 should be considered in the differential diagnosis of PNDM, especially in consanguineous families.

References

• Diabetes & metabolism • 2013 • Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family. PMID:23562494
• Journal of diabetes investigation • 2023 • MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra-pancreatic congenital defects presenting in severe diabetic ketoacidosis. PMID:36586106

Evidence Based Scoring (AI generated)