The Genotypic and Family Characteristics and Clinical Intervention of Neurofibromatosis type 1 Gene Are associated With Dystrophic Scoliosis by Whole-Exome Sequencing

Yukun Du¹Tianyu Bai¹Jie Song¹Li Zhang¹Hui Huang¹Peng Han²Fangfang Gai²Jianwei Guo¹Jianyi Li¹Changlin Lv¹Jiale Shao¹Guodong Zhang¹Hao Tao¹Yongming Xi^1*

• ¹The Affiliated Hospital of Qingdao University, Qingdao, China
• ²Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, China

Background: To investigate the genotypic and family genetic characteristics of neurofibromatosis type 1 patients associated with dystrophic scoliosis and to further explore the clinical efficiency of surgical intervention to these patients. Methods: A total of 7 NF-1 patients with dystrophic scoliosis and their 11 immediate relatives were included in this study who visited our hospital's spinal surgery department from January 2020 to December 2022. The outcomes were summarized by investigating the clinical and imaging parameters before and after the treatment. The whole-exome sequencing (WES) was conducted to analyze the genotypic and family genetic characteristics of all patients and their families. Results: Among the seven patients, six patients underwent surgical treatment after follow-up. Compared to preoperative Cobb angle, the maximum postoperative correction rate was 85.3%. We identified 8 pathogenic variants in the NF-1 gene. The variants c.c4084T and c.T4445C are located in the GAP-related domain and variant c.G1885A which was shared by patient 3 and his diseased brother. In the family of patient 3, variant c.G1885A was detected in both neurofibromatosis patients. The rs112819846 exhibited the most pronounced frequency disparity, whereas rs2916067 and rs80221306 were found among all patients. Conclusion: In this cohort, NF-1 patients with dystrophic scoliosis predominantly presented with upper thoracic involvement, and surgical correction achieved a maximum postoperative Cobb angle correction rate of 85.3% without loss of correction during follow-up. The c.G1885A variant in the NF-1 gene may influence the phenotypic severity of the disease, and the rs112819846, rs2916067 and rs80221306 may be the disease-relevant pathogenic variants of NF-1 patients with dystrophic scoliosis.