Genetic structure of partial gigantism syndromes and vascular malformations

Disorders of somatic mosaicism represent a heterogeneous group of conditions caused by postzygotic variants in genes regulating cell growth, proliferation, and angiogenesis. Their phenotypic manifestations are highly variable and often overlapping, making molecular genetic testing essential for accurate diagnosis and therapeutic decision-making. In this study, we applied a custom NGS panel targeting genes involved in overgrowth syndromes and vascular malformations to a cohort of patients with suspected PROS and other mosaic disorders. Pathogenic or likely pathogenic variants were detected in 65,8% of cases, indicating a high diagnostic efficiency of the developed panel. The variant allele frequency was generally below 20%, highlighting the need for high-depth sequencing to detect lowlevel mosaicism. The study also demonstrated the utility of this approach for differential diagnosis of mosaic overgrowth and vascular disorders beyond PROS. Thus, high-depth targeted NGS of the developed panel proved to be an effective tool for precision diagnostics, selection of targeted therapy, and expanding the genetic spectrum of mosaic disorders.

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