A novel variant of NF1 gene in a patient with neurofibromatosis type 1: a case report

Abstract

Background. neurofibromatosis type 1 is a common hereditary autosomal dominant disorder caused by pathogenic genetic variants in the NF1 gene located on chromosome 17q11.2. the disease is characterized by high allelic heterogeneity and the absence of clear genotypic correlations, with the exception of large deletions associated with a more severe phenotype. Clinically, neurofibromatosis is characterized by the presence of multiple (>6) "café-au-lait” spots, neurofibromas of any type or plexiform neurofibromas, freckles in the axillary or inguinal areas, hamartomatous Lisch nodules of the iris, optic glioma, and bone dysplasia. therefore, the description of each new genetic variant is essential for expanding the spectrum of known variants and improving molecular diagnostics. Case Report . the article describes a clinical and molecular genetic study of a 10-year-old boy. since early childhood, the patient has had multiple “café-au-lait” spots, speech impairment, grade 1 hypotrophy, rickets, sequelae of perinatal CNs damage, myotonic syndrome, and a delay in motor development. Magnetic resonance imaging of the brain revealed signs of focal damage to both hemispheres, the cerebellar vermis, and the left subcortical nuclei, and a glioma of the right optic nerve was detected. Neurofibromatosis type 1 was diagnosed based on clinical criteria. Whole-genome DNA sequencing was performed, followed by bioinformatics analysis and confirmation of the results by direct sanger sequencing. A previously undescribed complex, likely pathogenic variant NM_001042492.3:c.40 60_4068delinsC of the NF1 gene was identified in the heterozygous state. this variant leads to a reading frameshift and premature translation termination after the synthesis of 23 amino acids (p.ser1354Leufs*23). this variant is not present in available population genetic variant databases. Conclusion. thus, wholegenome sequencing identified a new pathogenic variant in the NF1 gene associated with the development of neurofibromatosis type 1. the obtained data expand the range of variants for this pathology and can be used in medical genetic counseling, as well as in algorithms for molecular genetic diagnostics of patients with suspected neurofibromatosis type 1.