两处基因杂合突变的 I型神经纤维瘤病 1例

目的探究脊柱侧弯伴全身多发牛奶咖啡斑的 Ⅰ型神经纤维瘤病( NF1)病儿的致病原因。方法男， 7岁，因全身多发牛奶咖啡斑 7年、脊柱侧弯 6个月于 2022年 10月就诊河北医科大学第三医院。诊断为 NF1。应用全外显子高通量测序和 Sanger测序分别对变异位点进行筛选和验证。结果病儿 NF1基因 c.2033delC(exon18，NM_000267)导致氨基酸改变 p. P678Rfs*10，为移码突变，为已报道的致病突变； c.2029C>A(exon18，NM_000267)导致氨基酸改变 p.P677T，为错义突变，为可能致病性变异。结论 NF1基因 c.2033delC是导致 Ⅰ型神经纤维瘤病的原因，基因 c.2029C>A拟进一步扩充 NF1基因变异谱，其是否能独立致病、能否影响该病的严重程度，值得临床医师的深入研究和验证。

A case of type I neurofibromatosis with two heterozygous mutations

Objective To explore the cause of NF1 in a child with café-au-lait spots and scoliosis.Methods A7-year-old male pa- tient was admitted to the Third Hospital of Hebei Medical University in October 2022 due to multiple café-au-lait spots throughout his body for 7 years and scoliosis for 6 months.The diagnosis was NF1. Whole-exon high-throughput sequencing and Sanger sequencing were applied to screen and verify the variant sites,respectively.Results The patient''s NF1 gene,c.2033delC (exon18,NM_000267),resulted in amino acid change p.P678Rfs*10,a code-shifting mutationand a reported pathogenic mutation,and c.2029C>A (exon18,NM_000267),resulted in amino acid change p.P677T,a missense mutation and a likely pathogenic variant.Conclusions The NF1gene c.2033delC isthe cause of neurofibromatosis type 1. Gene c.2029C>A intends to further expand the variation spectrum of NF 1 gene. Whether it cancause the disease independently and affect the severity of the disease is worth in-depth study and verification by clinicians.