一个以高血压、骨折为首发症状的Ⅰ型神经纤维瘤病家系分析  

Pedigree analysis of a neurofibromatosis type 1 family with early-onset of fracture and hypertension

作　　者：苏赟 毛澄源[1] 秦小飞[2] 单迎光[2] 史长河[1] 范丽媛 董亚丽 郑惠敏[1] 李心蔚 张槊 胡正威[1] 杨靖[1] 许予明[1] SU Yun;MAO Chengyuan;QIN Xiaofei;SHAN Yingguang;SHI Changhe;FAN Liyuan;DONG Yali;ZHENG Huimin;LI Xinwei;ZHANG Shuo;HU Zhengwei;YANG Jing;XU Yuming(Department of Neurology,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Department of Cardiovasology,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Henan Key Laboratory for Pharmacology of Liver Diseases,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院神经内科,郑州450052 [2]郑州大学第一附属医院心血管内科,郑州450052 [3]河南省肝病药理重点实验室,郑州450052

出　　处：《郑州大学学报（医学版）》2022年第5期658-662,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金项目(U1904207,91849115,81771290,81974211,81901300);国家重点研发计划项目(2017YFA0105003);中国医学科学院中央级公益性科研院所基本科研业务费专项资金资助项目(2020-PT310-01);河南省科技攻关项目(SBGJ202003020);河南省中青年卫生健康科技创新优秀青年人才培养项目(YXKC2021062)。

摘　　要：目的:报道一个临床表现不典型的Ⅰ型神经纤维瘤病家系,并确定其致病突变。方法:收集先证者临床资料。提取先证者及父母外周全血基因组DNA,应用目标捕获高通量测序技术对neurofibromin 1(NF1)基因全部编码区外显子及其侧翼序列进行突变检测,对可疑位点进行Sanger测序。结果:先证者男性,12岁,以右侧股骨骨折为首发症状,合并高血压病(3级,低危);查体示胸腹部呈弥漫大片状深棕色牛奶咖啡斑,MRI提示神经纤维来源肿瘤及腰椎骨质破坏。先证者母亲有类似皮肤病变,无其他自觉症状。先证者及其母均检出NF1基因第38号外显子存在杂合移码突变c.5719delG(p.Glu1907Lysfs*14),表型正常的父亲未检测到此突变。该突变在HGMD和ExAC数据库中均未有报道,为新发突变。结论:NF1基因c.5719delG(p.Glu1907Lysfs*14)移码杂合突变是该家系患病的遗传学病因。Aim:To report a family with neurofibromatosis type 1 presenting with atypical manifestations and identify the pathogenic variant.Methods:The clinical data of the proband was collected.Genomic DNA was extracted from the peripheral blood of the proband and his parents,screened by targeted high-throughput sequencing of the coding exons and the flanking sequences of neurofibromin 1(NF1)gene,and the suspected mutation site was validated by Sanger sequencing.Results:The proband,a 12-year-old boy,initially presented with fracture of the right femur and hypertension(grade 3,low risk).Physical examination demonstrated the café-au-lait macules manifested as large patch and dark brown in the thoracic and abdominal region.MRI showed soft tissue mass of suspected neurofibroma and bone destruction in the lumbar vertebra.The proband's mother exhibited similar skin lesions,without other subjective symptoms.A heterozygous frameshift mutation of c.5719delG(p.Glu1907Lysfs*14)in the exon 38 of NF1 gene was detected in the proband and his mother,but not detected in his asymptomatic father.The variant is a novel mutation which has not been reported in HGMD or ExAC databases.Conclusion:The heterozygous frameshift mutation of c.5719delG(p.Glu1907Lysfs*14)in NF1 gene is the genetic variant of this family with neurofibromatosis type 1.

关 键 词：Ⅰ型神经纤维瘤病 目标捕获高通量测序技术 NF1基因 

分 类 号：R739.4[医药卫生—肿瘤]