两例散发1型神经纤维瘤病合并肾病综合征患儿的遗传学分析  

Genetic analysis of two children with sporadic neurofibromatosis type 1 complicated with nephrotic syndrome

作　　者：刘竹枫[1] 王文红[1] 郭珍[2] 赵林胜[3] 吴瑕[2] 刘涛[1] 韩婷婷 Liu Zhufeng;Wang Wenhong;Guo Zhen;Zhao Linsheng;Wu Xia;Liu Tao;Han Tingting(Department of Nephrology,Tianjin Children′s Hospital(Tianjin University Children′s Hospital),Tianjin 300074,China;Department of Ophthalmology,Tianjin Children′s Hospital(Tianjin University Children′s Hospital),Tianjin 300074,China;Department of Pathology,Tianjin Children′s Hospital(Tianjin University Children′s Hospital),Tianjin 300074,China)

机构地区：[1]天津市儿童医院(天津大学儿童医院)肾脏科,天津300074 [2]天津市儿童医院(天津大学儿童医院)眼科,天津300074 [3]天津市儿童医院(天津大学儿童医院)病理科,天津300074

出　　处：《中华医学遗传学杂志》2022年第12期1349-1353,共5页Chinese Journal of Medical Genetics

基　　金：天津市卫计委科技基金项目 (ZC20088)。

摘　　要：目的:探讨两例散发1型神经纤维瘤病(neurofibromatosis type 1,NF1)合并肾病综合征(nephrotic syndrome,NS)患儿的遗传学病因。方法:收集患儿的临床资料,通过高通量测序技术对患儿进行基因变异检测,并用Sanger测序对候选变异进行验证。结果:两例患儿临床均表现出牛奶咖啡斑、腋窝下雀斑和眼部Lisch结节等,患儿1伴左下肢先天性胫腓假关节。基因检测结果显示患儿1的NF1基因第8外显子存在c.844C>T杂合变异,患儿2的NF1基因第11外显子存在c.1246C>T杂合变异,均被诊断为NF1。两例患儿分别在3岁和10岁出现了大量蛋白尿、低白蛋白血症、高胆固醇血症及指凹性水肿,均符合NS临床表型,且患儿2为微小病变肾病。患儿1给予糖皮质激素治疗,患儿2给予糖皮质激素联合霉酚酸酯治疗,NS病情均有缓解,随访1年,无复发。结论:NF1合并NS在临床较为罕见,儿童NF1合并微小病变肾病的预后相对良好,NF1基因的检测有助于NF1的早期筛查和诊断。Objective To explore the genetic basis for two children with sporadic neurofibromatosis type 1(NF1)complicated with nephrotic syndrome(NS).Methods Clinical data of the children were collected.Both children were subjected to high-throughput sequencing,and candidate variants were verified by Sanger sequencing.Results Both children had café-au-lait macules,subaxillary freckle and Lisch nodules.Child 1 also had congenital tibiofibular pseudarthrosis on the left side.Genetic testing revealed that child 1 has harbored a heterozygous c.844C>T variant in the exon 8 of the NF1 gene,whilst child 2 has harbored a heterozgyous c.1246C>T variant in the exon 11 of the NF1 gene.Both children were diagnosed with NF1 and have developed pronounced proteinuria,hypoalbuminemia,hypercholesterolemia and pitting edema at the ages of 3 and 10,respectively.Renal biopsy of child 2 has revealed minimal change nephropathy,and the diagnosis of nephrotic syndrome was established.Child 1 was treated with glucocorticoid,and child 2 was treated with glucocorticoid in combination with mycophenolate mofetil.The NS was relieved with no recurrence during 1 year′s follow-up.Conclusion NF1 combined with NS is rare in the clinical settings.The prognosis of children with NF1 combined with minimal change nephropathy is relatively good.Detection of NF1 gene variant can facilitate early identification and diagnosis of NF1.

关 键 词：1型神经纤维瘤病 NF1基因 肾病综合征 

分 类 号：R739.4[医药卫生—肿瘤] R726.9[医药卫生—临床医学]