Analysis of clinical manifestations of neurofibromatosis type 1 in patients with in-frame mutations in the NF1 gene from the Republic of Bashkortostan

Background. Neurofibromatosis type 1 (NF1) is a genetic disorder that is characterized by multiple light brown patches of skin (café-au-lait spots) and neurofibromas. It can lead to an increased risk of malignant tumors, cognitive impairment, and skeletal abnormalities. NF1 is caused by heterozygous mutations in the NF1 gene, and identifying the specific mutation can form the basis for pathogenetic treatment of tumor syndrome. Several studies indicate that patients with the NF1 in-frame deletions tend to have a milder form of the disease that is characterized by the absence of neurofibromas. the purpose of the study was to identify in-frame deletions in the NF1 gene in patients from the Republic of Bashkortostan as well as to characterize the clinical symptoms of NF1 in this group of patients.

Material and Methods. An analysis of outpatient records of NF1 patients from the Republic of Bashkortostan was conducted, along with an objective clinical examination of the patients and DNA sequencing to identify in-frame deletions in the NF1 gene. Twenty-six patients (12 females and 14 males) aged 3 to 69 years were studied.

Results. The retrospective analysis of outpatient records and examination of NF1 patients showed the NF1 incidence of 1:7403.6 people. Two in-frame deletions in the NF1 gene were identified in 6 patients with NF1 from 3 unrelated families: NF1:NM_000267.3:exon21:c.2674_2679del:p. S892_K893del; NF1:NM_000267.3:exon27:c.3526_3528delAGA:p.Arg1176del. The clinical manifestations of NF1 in patients with identified mutations and their comparative characteristics with all NF1 patients in the Republic were described. In the general group of NF1 patients from the Republic, a rarer detection of neurofibromas and malignant tumors, optic nerve gliomas, and cognitive impairment was revealed.

Conclusion. In patients with NF1 from the Republic of Bashkortostan with in-frame deletions in the NF1 gene, no brain cysts or tumors, plexiform neurofibromas, and optic nerve gliomas were detected. Although the mutations we identified have not previously been described in the scientific literature, our analysis of clinical features is consistent with the findings of other authors regarding the presence of phenotypic correlations with in-frame deletions.

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