OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

A large intrathoracic meningocele, a saccular protrusion of the meninges through a dilated intervertebral foramen or a bony defect of the vertebral column, was diagnosed in a 41-year-old female patient showing clinical features of neurofibromatosis-1 (NF-1), including cafe-au-lait spots, cutaneous neurofibromas, and axillary frecklings and Lisch nodules on the iris. Her daughter and son also had similar manifestations of NF-1. Regular follow-up with periodic imaging was recommended without surgical treatment because there were no signs or symptoms. Meningocele should be differentiated from posterior mediastinal tumors such as neurofibroma, neuroblastoma, and ganglioneuroma because NF-1 has a high risk of tumor formation. We report on this case with a brief review of the literature.
Adult ; Diagnosis, Differential ; Female ; Humans ; Incidental Findings ; Meningocele/*complications/*pathology ; Neurofibromatosis 1/*complications/genetics/*pathology ; Pedigree

Antineoplastic Agents ; therapeutic use ; Benzamides ; Drug Resistance, Neoplasm ; Exons ; Gastrointestinal Stromal Tumors ; drug therapy ; metabolism ; pathology ; Humans ; Imatinib Mesylate ; Mutation ; Neurofibromatosis 1 ; metabolism ; pathology ; Omentum ; Peritoneal Neoplasms ; metabolism ; pathology ; Piperazines ; therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Pyrimidines ; therapeutic use

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders in humans. NF1 is caused by mutations in the NF1 gene which consists of 57 exons and encodes a GTPase activating protein (GAP), neurofibromin. To date, more than 640 different NF1 mutations have been identified and registered in the Human Gene Mutation Database (HGMD). In order to assess the NF1 mutational spectrum in Korean NF1 patients, we screened 23 unrelated Korean NF1 patients for mutations in the coding region and splice sites of the NF1 gene. We have identified 21 distinct NF1 mutations in 22 patients. The mutations included 10 single base substitutions (3 missense and 7 nonsense), 10 splice site mutations, and 1 single base deletion. Eight mutations have been previously identified and thirteen mutations were novel. The mutations are evenly distributed across exon 3 through intron 47 of the NF1 gene and no mutational hot spots were found. This analysis revealed a wide spectrum of NF1 mutations in Korean patients. A genotype- phenotype correlation analysis suggests that there is no clear relationship between specific NF1 mutations and clinical features of the disease.
Adolescent ; Adult ; Child ; Child, Preschool ; DNA/chemistry/genetics ; DNA Mutational Analysis ; Genotype ; Humans ; Infant ; Korea ; Middle Aged ; *Mutation ; Neurofibromatosis 1/*genetics/pathology ; Neurofibromin 1/*genetics ; Phenotype ; Research Support, Non-U.S. Gov't

Adult ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Neurofibromatosis 1 ; genetics ; pathology