目的 对1例疑为尼曼匹克病C型的患儿进行临床和遗传学分析.方法 采用新一代测序技术对患儿进行基因变异分析,并对疑似致病性变异进行患儿及其父母的Sanger测序验证及生物信息学预测,用SIFT、PolyPhen-2和MutationTaste软件对新变异进行致病性分析.结果 基因测序发现患儿NPC1基因存在c.2728G>A(p.G910S)和c.269C>G(p.P90R)复合杂合变异,分别遗传自其母亲和父亲.NPC1基因c.2728G>A(p.G910S)变异为HGMD报道的已知致病性变异,c.269C>G(p.P9oR)变异目前未见文献报道,生物信息学预测为致病性变异.结论 患儿为NPC1基因复合杂合变异引起的尼曼匹克病C型,该发现丰富了NPC1基因变异谱,并为家系遗传咨询及产前诊断提供了依据.
Objective To delineate the clinical and genetic features of a Chinese boy suspected for Niemann-Pick disease type C.Methods The patient underwent clinical examination and was subjected to next generation sequencing.Suspected mutations were validated by Sanger sequencing.Potential impact of the novel mutation was predicted by SIFT,PolyPhen-2 and Mutation Taste software.Results The child has featured hepatosplenomegaly,increased direct bilirubin,jaundiced skin and liver damage.DNA sequencing showed that he has carried compound heterozygous mutations of NPC1 gene,namely c.2728G>A(p.G910S)and c.269C>G(p.P90R),which were inherited from his mother and father,respectively.The c.2728G>A(p.G910S)mutation was previously reported,while the c.269C>G(p.P90R)was a novel mutation.Conclusion The child has suffered from Niemann-Pick disease type C due to mutations of NPC1 gene.This finding has enriched the spectrum of NPC1 mutations and provided a basis for genetic counseling and prenatal diagnosis.
Chinese Journal of Medical Genetics
Niemann-Pick disease type C
Next generation sequencing