To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.

To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.