神经纤维瘤病Ⅰ型一家系临床特点及基因突变分析

A family of neurofibromatosis type Ⅰ: a clinical feature and gene mutation analysis

目的总结神经纤维瘤病Ⅰ型(NF1)一家系的临床表型及NF1基因突变特点。方法收集2020年5月郑州大学附属儿童医院神经内科确诊为NF1的一家系临床资料,总结先证者及家系成员临床特征。同时采用二代测序方法对先证者行NF1/NF2基因panel测序,并对家系成员进行一代Sanger测序验证分析,分析其基因突变特点。结果先证者(Ⅴ_(2))为1岁2个月女童,临床表型为出生时全身皮肤多个咖啡牛奶斑,精神及运动发育正常,婴儿期出现局灶性癫痫发作。家系中父亲(Ⅳ_(3))、祖母(Ⅲ_(2))及其他2人(Ⅱ_(2)、Ⅰ_(2))均有皮肤咖啡牛奶斑或神经纤维瘤、无癫痫发作。其母亲表型正常。先证者NF1基因突变表现为c.83-84delAG(P.N29Hfs*8),属于未报道的移码杂合突变;Sanger测序验证其父亲及祖母NF1基因突变类型与先证者一致,符合NF1杂合突变常染色显性遗传特点。结论NF1由NF1基因突变引起,早期临床表现多为牛奶咖啡斑,部分有癫痫发作,疑似患者应尽早行基因分析确诊。

Objective To summarize the clinical features of a family of neurofibromatosis type I(NF1)and its NF1 gene mutation characteristics.Methods The clinical data of a family of NF1 admitted to our hospital in May 2020 were collected.The proband was sequenced with NF1/NF2 panel using second-generation sequencing.Sanger sequencing verification analysis was performed on the family members.The clinical characteristics of the proband and other family members were summarized and their gene mutations were analyzed.Results The proband(V2),a 1-year and 2-month old girl,had multiple Cafeau lait spots on the skin at birth,normal mental and motor development,and focal epileptic seizures in infancy.The father(IV_(3)),grandmother(III_(2)),and other 2 family members(II_(2),I_(2))in the family all had Cafeau lait spots or neurofibromatous changes without seizures.The mother's phenotype was normal.The proband had a heterozygous mutation in the NF1 gene,and the mutation site C.83-84delAG(P.N29Hfs*8)was a frameshift heterozygous mutation.After verification analysis by Sanger sequencing,the pathogenic genes of the father and grandmother were consistent with the proband,which was in line with the characteristics of heterozygous mutation in NF1 gene,dominant inheritance.Conclusion NF1 is caused by NF1 gene mutation;the early clinical manifestations mostly include café-au-lait spots,and some have seizures;patients with multiple café-aulait spots with seizures should be diagnosed by genetic analysis as soon as possible.