Rare BLK, CEL, KLF11, PDX1, and PAX4 Gene Variants in Russian Patients with Monogenic Diabetes: Clinical and Molecular Characterization

<b>Background:</b> Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic diabetes forms that are frequently misclassified as type 1 or type 2 diabetes due to overlapping phenotypic features. The true prevalence of MODY is likely substantially underestimated. As DNA-based diagnostics become increasingly accessible, an expanding number of novel genetic variants are being identified. <b>Objectives:</b> The aim of this study was to characterize the clinical and genetic features of patients carrying rare variants in the <i>BLK</i>, <i>KLF11</i>, <i>PAX4</i>, <i>PDX1</i>, and <i>CEL</i> genes, with attention to population-specific aspects, family history, and treatment outcomes. <b>Methods:</b> Targeted next-generation sequencing (NGS) using a custom-designed panel covering 27 genes implicated in MODY, neonatal diabetes, and related hereditary syndromes was performed on the Illumina NovaSeq 6000 platform (Illumina). <b>Results:</b> We identified 21 variants in five genes associated with rare MODY subtypes among 24 unrelated patients. MODY9 was diagnosed in two unrelated patients of Russian ethnicity harboring an identical heterozygous missense mutation in exon 5 of the <i>PAX4</i> gene (HG38, chr7:127615049G>A, c.191C>T, p.Thr64Ile), which has not been previously described in patients with diabetes. MODY11 was diagnosed in a patient carrying the c.773-1G>A variant in the <i>BLK</i> gene. A patient with a de novo c.40_41dupGC (p.Val15Glnfs*41) variant in the <i>KLF11</i> gene was clinically diagnosed with type 1 diabetes. <b>Conclusion:</b> Our findings expand the current understanding of rare MODY subtypes and contribute to the growing body of evidence on the spectrum and frequency of potentially pathogenic variants in <i>BLK</i>, <i>CEL</i>, <i>KLF11</i>, <i>PDX1</i>, and <i>PAX4</i> genes across ethnically diverse populations worldwide.