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Journal of Neurology

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14.12.2023 | Original Communication

Genotype–phenotype correlations of neurofibromatosis type 1: a cross-sectional study from a large Chinese cohort

verfasst von: Beiyao Zhu, Tingting Zheng, Wei Wang, Yihui Gu, Chengjiang Wei, Qingfeng Li, Zhichao Wang

Erschienen in: Journal of Neurology | Ausgabe 4/2024

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Abstract

Background

Neurofibromatosis type 1 (NF1) is a highly heterogeneous autosomal genetic disorder characterized by a broad spectrum of clinical and molecular manifestations. The correlations between genotype and phenotype in NF1 remain elusive. This study aimed to elucidate genotype–phenotype associations in a large Chinese cohort of NF1 patients.

Methods

We included NF1 patients from our center who underwent genetic testing for NF1 variants and systemic examination. Genotype–phenotype correlation analyses were performed, focusing on variation types and involved neurofibromin domains.

Results

A total of 195 patients were enrolled, comprising 105 males and 90 females, with a median age of 18 years. Truncating variants, single amino acid variations, and splicing variants accounted for 139/195 (71.3%), 23/195 (11.8%), and 33/195 (16.9%), respectively. Patients with splicing variants exhibited a significantly higher prevalence of spinal plexiform neurofibromas (spinal PNF) than those with truncating variants (76.4% vs. 51.8%; p = 0.022). Variations affecting the PKC domain were associated with higher rates of cutaneous neurofibromas (CNF) (100% vs. 64.9%, p < 0.001), Lisch nodules (100% vs. 61.2%, p < 0.001), plexiform neurofibromas (PNF) (100% vs. 95.7%, p = 0.009), and psychiatric disorders (11.8% vs. 1.6%, p = 0.042). Patients with mutations in the CSRD had an elevated risk of secondary primary malignancies (11.6% vs. 2.8%, p = 0.015). GRD involvement might enhance the risk of Lisch nodules (76.9% vs. 53.7%, p = 0.044). Variations in the Sec14-PH domain were correlated with a higher rate of CNF (76.8% vs. 58.6%, p = 0.014). Additionally, we found that the p.R1748* variants carry a high risk of malignancy.

Conclusion

Our study suggested some novel genotype–phenotype correlations within a Chinese cohort, providing innovative insights into this complex field that may contribute to genetic counseling, risk stratification, and clinical management for the NF1 population.

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Titel: Genotype–phenotype correlations of neurofibromatosis type 1: a cross-sectional study from a large Chinese cohort
verfasst von: Beiyao Zhu
Tingting Zheng
Wei Wang
Yihui Gu
Chengjiang Wei
Qingfeng Li
Zhichao Wang
Publikationsdatum: 14.12.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 4/2024
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-023-12127-w

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