表型温和的1型神经纤维瘤病：5个家系基因突变分析

【摘要】 目的 检测表型温和的1型神经纤维瘤病（NF1）患者的基因突变。方法 2017年6月至2020年6月于上海市奉贤区皮肤病防治所皮肤科门诊收集5例表型温和、仅有皮损的NF1先证者及其家系成员，在家系调查的基础上，观察和记录NF1的临床表型，并利用二代靶向基因测序结合Sanger测序来检测和验证致病突变。结果 5例先证者都仅有皮损（包括咖啡斑、雀斑、神经纤维瘤），无其他系统损害；5个家系先证者共发现5种突变，分别位于NF1基因的不同外显子中，包括1个大片段缺失突变（hg38：chr17：31327199-31335928 del 8 730 bp）、1个剪切突变（c.7970+1G>T）、1个插入突变（c.3011 _3012insTATG，p.N1004fs*）、1个缺失突变（c.1754_1757delTAAC， p.T586Vfs*18）和1个无义突变（c.C503G，p.S168X），前3种是未经报道的新突变。结论 在5个先证者表型温和的NF1家系中检测出5种突变，鉴定出3种新突变，丰富了NF1的突变谱。

Mutation analysis in 5 families with mild phenotypes of neurofibromatosis type 1

【Abstract】 Objective To detect gene mutations in patients with mild phenotypes of neurofibromatosis type 1 （NF1）. Methods From June 2017 to June 2020, 5 probands with mild phenotypes of NF1 only involving lesions and their family members were collected from Department of Dermatology, Fengxian Institute of Dermatosis Prevention and Treatment in Shanghai. Pedigree investigation was performed to evaluate the clinical phenotypes of NF1. The second-generation targeted gene sequencing combined with Sanger sequencing was performed to detect and verify pathogenic mutations. Results All the 5 probands only presented with skin lesions, including café-au-lait spots, freckles, neurofibromas, without other systemic involvement. A total of 5 mutations were identified in different exons of the NF1 gene in the 5 families, including 1 large-fragment deletion mutation （hg38: chr17:31327199-31335928 del 8 730 bp）, 1 splicing mutation （C.7970+1G>T）, 1 insertion mutation （C.3011_3012insTATG, p.N1004fs*）, 1 deletion mutation （C.1754_1757delTAAC, p.T586Vfs*18）, and 1 nonsense mutation （c.C503G, p.S168X）, and the first 3 above mentioned mutations were unreported novel mutations. Conclusion Five mutations were identified in the 5 families with mild phenotypes of NF1, including 3 novel mutations, which expand the mutational spectrum of NF1.