Analysis of Clinical Manifestations of Neurofibromatosis Type 1 in Patients with Nonsense Pathogenic Variants in the NF1 Gene from the Republic of Bashkortostan

Relevance: neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome occurring with a frequency of 1:3164. NF1 is characterized by severe clinical manifestations with multiple cutaneous and subcutaneous tumors, plexiform neurofibromas, skeletal abnormalities and cognitive disorders. The study of the genetic causes of NF1 can become the basis for prenatal diagnosis and the use of new methods of treating the disease. Materials and methods: clinical and epidemiological study of NF1 patients in the Republic of Bashkortostan, sequencing the NF1 gene in their DNA samples as well as whole genome sequencing using the WGS method. To search for the pathogenic variants we found in publications by other authors, we analyzed the Scopus, WoS, ClinVar, PubMed, and SNP databases. Results: the frequency of occurrence of NF1 in the republic is 1:7407. 23 nonsense pathogenic variants in 21 exons of the NF1 gene were identified in 39 NF1 patients from 26 families. Discussion and conclusion: the frequency of development of the main clinical manifestations of NF1 in patients from the republic corresponds to data from around the world, however, plexiform neurofibromas, optic nerve gliomas, short stature and decreased intelligence were detected significantly less frequently. Of the 23 nonsense pathogenic variants we identified, 16 pathogenic variants were previously described by researchers from various countries, and 7 pathogenic variants: NM_001042492.3:c.55G>T (NP_001035957.1:p.Glu19Ter), NM_001042492.3:c.2806A>T (NP_001035957.1:p.Lys936Ter), NM_001042492.3:c.3284T>A ( NP_001035957.1:p.Leu1095Ter), NM_001042492.3:c.5014G>T ( NP_001035957.1:p.Gly1672Ter), NM_001042492.3:c.5242C>T (NP_001035957.1:p.Arg1748Ter), NM_001042492.3:c.7365T>G (NP_001035957.1:p.Tyr2455Ter) and NM_001042492.3:c.7482G>A (NP_001035957.1:p.Trp2494Ter) have been identified for the first time in the word. Patients with nonsense pathogenic variants have significantly higher rates of brain tumors and epilepsy compared to all NF1 patients in the republic.