Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort
Abstract Background To identify the genetic variants underlying neurofibromatosis type 1 (NF1) and to investigate genotype-phenotype correlations. Methods Thirty-three patients from 27 Chinese pedigrees with suspected NF1 phenotypes underwent genetic analysis. The impact of splicing variant on NF1 m...
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BMC
2025-05-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03807-z |
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| author | Hongjun Fei Xu Han Yiyao Chen Yan Xu Chunxin Chang Ming Li Yanlin Wang Jian Wang Niu Li Shuyuan Li |
| author_facet | Hongjun Fei Xu Han Yiyao Chen Yan Xu Chunxin Chang Ming Li Yanlin Wang Jian Wang Niu Li Shuyuan Li |
| author_sort | Hongjun Fei |
| collection | DOAJ |
| description | Abstract Background To identify the genetic variants underlying neurofibromatosis type 1 (NF1) and to investigate genotype-phenotype correlations. Methods Thirty-three patients from 27 Chinese pedigrees with suspected NF1 phenotypes underwent genetic analysis. The impact of splicing variant on NF1 mRNA processing was determined by cDNA direct sequencing. Additional NF1 patients with detailed clinical and molecular data were extracted from the literature for performing genotype-phenotype correlation analysis. Results Genetic analysis identified 24 distinct NF1 variants: nine frameshift, four nonsense, four missense, six splice site, and one exon deletion. Among them, 10 were previously unreported in the literature. A functional study showed that the canonical splicing variant (c.3497–2 A > G) resulted in an in-frame deletion of two amino acids, which may not affect protein function. Finally, 22 variants were classified as pathogenic or likely pathogenic. After evaluation of the clinical data and genetic evidence, the diagnoses of 31 patients from 25 families were confirmed. Genotype–phenotype correlation analysis from the cohort, consisting of 28 patients in this study and 235 published cases, showed that the onset of neurofibromas and bone lesions exhibited an age-dependent association, with 79.8% and 73.8% probability of developing in patients older than 23.5 years or 20.5 years, respectively. No association was found between the location or type of NF1 variants and any specific features. Conclusions We comprehensively described the clinical and genetic data of a Chinese NF1 cohort and emphasized the necessity of further functional analysis on splicing variants. Neurofibromas and bone lesions are age-dependent disease complications that exhibit progressive tendencies with increasing age in patients with NF1. |
| format | Article |
| id | doaj-art-572ccf2965e64873a2215ae5bcc1b41e |
| institution | OA Journals |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-572ccf2965e64873a2215ae5bcc1b41e2025-08-20T01:53:19ZengBMCOrphanet Journal of Rare Diseases1750-11722025-05-0120111110.1186/s13023-025-03807-zGenetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohortHongjun Fei0Xu Han1Yiyao Chen2Yan Xu3Chunxin Chang4Ming Li5Yanlin Wang6Jian Wang7Niu Li8Shuyuan Li9The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineThe International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University school of MedicineAbstract Background To identify the genetic variants underlying neurofibromatosis type 1 (NF1) and to investigate genotype-phenotype correlations. Methods Thirty-three patients from 27 Chinese pedigrees with suspected NF1 phenotypes underwent genetic analysis. The impact of splicing variant on NF1 mRNA processing was determined by cDNA direct sequencing. Additional NF1 patients with detailed clinical and molecular data were extracted from the literature for performing genotype-phenotype correlation analysis. Results Genetic analysis identified 24 distinct NF1 variants: nine frameshift, four nonsense, four missense, six splice site, and one exon deletion. Among them, 10 were previously unreported in the literature. A functional study showed that the canonical splicing variant (c.3497–2 A > G) resulted in an in-frame deletion of two amino acids, which may not affect protein function. Finally, 22 variants were classified as pathogenic or likely pathogenic. After evaluation of the clinical data and genetic evidence, the diagnoses of 31 patients from 25 families were confirmed. Genotype–phenotype correlation analysis from the cohort, consisting of 28 patients in this study and 235 published cases, showed that the onset of neurofibromas and bone lesions exhibited an age-dependent association, with 79.8% and 73.8% probability of developing in patients older than 23.5 years or 20.5 years, respectively. No association was found between the location or type of NF1 variants and any specific features. Conclusions We comprehensively described the clinical and genetic data of a Chinese NF1 cohort and emphasized the necessity of further functional analysis on splicing variants. Neurofibromas and bone lesions are age-dependent disease complications that exhibit progressive tendencies with increasing age in patients with NF1.https://doi.org/10.1186/s13023-025-03807-zNeurofibromatosis type 1Novel variantsGenotype–phenotypeNeurofibromasBone lesions |
| spellingShingle | Hongjun Fei Xu Han Yiyao Chen Yan Xu Chunxin Chang Ming Li Yanlin Wang Jian Wang Niu Li Shuyuan Li Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort Orphanet Journal of Rare Diseases Neurofibromatosis type 1 Novel variants Genotype–phenotype Neurofibromas Bone lesions |
| title | Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort |
| title_full | Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort |
| title_fullStr | Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort |
| title_full_unstemmed | Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort |
| title_short | Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort |
| title_sort | genetic analysis of 25 chinese pedigrees with neurofibromatosis type 1 and genotype phenotype study from an extended cohort |
| topic | Neurofibromatosis type 1 Novel variants Genotype–phenotype Neurofibromas Bone lesions |
| url | https://doi.org/10.1186/s13023-025-03807-z |
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