Futagawa Mashu, Okazaki Tetsuya, Nakata Eiji, Fukano Chika, Osumi Risa, Kato Fumino, Urakawa Yusaku, Yamamoto Hideki, Ozaki Toshifumi, Hirasawa Akira
Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Orthopedic Surgery, Okayama University Hospital, Okayama, Japan.
Hum Genome Var. 2024 Nov 26;11(1):42. doi: 10.1038/s41439-024-00299-4.
Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care.
1型神经纤维瘤病（NF1）具有广泛的临床表现，包括肿瘤发生风险增加和高血压。关于NF1患者基因型与表型相关性的全面数据有限。因此，在本研究中，我们旨在阐明遗传性肿瘤队列中NF1的详细遗传和临床特征。我们在临床实验室进行了测序和拷贝数分析，并分析了44例疑似NF1患者的临床数据。在36例患者（81.8%）中检测到种系致病性变异，其中20.7%的变异是新发现的。值得注意的是，40.0%的成年患者患有恶性肿瘤；20.0%的患者发生女性乳腺癌，这一比例高于先前报道。30.6%的成年患者观察到高血压，1例患者猝死，另1例发展为嗜铬细胞瘤。3例NF1基因大片段缺失的患者表现出明显的皮肤、骨骼和神经学表现。这些结果突出了定期监测的重要性，特别是对于患有恶性肿瘤和高血压的患者。我们的研究结果为遗传咨询和临床管理提供了有价值的见解，强调了与NF1相关的多种健康风险以及全面多学科护理的必要性。
