Abstract
Background/Objectives: This study presents the first molecular characterization of NF1 gene variants in Kazakhstani patients, expanding regional understanding of neurofibromatosis type 1 (NF1). The NF1 gene encodes neurofibromin, a tumor suppressor protein that regulates the MAPK signaling pathway; its inactivation results in NF1, a multisystem disorder with pigmentary and tumor manifestations. Methods: A total of 60 pediatric and young adult patients of University Clinic Aksai were selected based on Legius criteria and studied clinically; genetic variants of NF1 gene were determined with AmpliSeq for Illumina Myeloid Panel (next generation sequencing). Results: Pathogenic or likely pathogenic (with some variants of unknown significance) were detected in 58 of 60 (96.7%) patients. Among them, 27 (46.6%) carried point variants, 21 (36.2%) had genomic deletions, 3 (5.2%) had duplications, 3 (5.2%) insertions, and 4 (6.9%) had exon–intron splicing site variants. Notably, all patients with duplication insertions and splicing variants presented with plexiform neurofibromas. Conclusions: The study defines the first variant spectrum in a Kazakhstani population, confirming genotype–phenotype correlations consistent with European cohorts (l.). These data highlight the predominance of structural and splicing alterations in patients with plexiform neurofibromas and support the integration of molecular testing into clinical management of NF1 in Kazakhstan.