1例由NPC1突变引起的C型尼曼-匹克病

[Niemann-Pick disease type C caused by NPC1 mutation in a case].

作者信息

Zhang Guangye, Yu Fengling, Zhang Kaihui, Li Fu, Lyu Yuqiang, Gao Min, Gai Zhongtao, Liu Yi

机构信息

Jinan Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Jinan, Shandong 250022, China. Email:

Clinical Laboratory, Qilu Children's Hospital of Shandong University, Jinan, Shandong 250022, China; Department of Hematology, Qilu Children's Hospital of Shandong University, Jinan, Shandong 250022, China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 May 10;36(5):480-483. doi: 10.3760/cma.j.issn.1003-9406.2019.05.016.

DOI:10.3760/cma.j.issn.1003-9406.2019.05.016

PMID:31030438

Abstract

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 MutationTaster 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. Above finding has enriched the spectrum of NPC1 mutations and provided a basis for genetic counseling and prenatal diagnosis.

摘要

目的

明确一名疑似患C型尼曼-匹克病的中国男孩的临床及基因特征。

方法

对该患者进行临床检查，并进行二代测序。通过桑格测序验证疑似突变。利用SIFT、PolyPhen-2和MutationTaster软件预测新突变的潜在影响。

结果

该患儿有肝脾肿大、直接胆红素升高、皮肤黄疸及肝损伤表现。DNA测序显示其携带NPC1基因的复合杂合突变，即c.2728G<A（p.G910S）和c.269C>G（p.P90R），分别遗传自其母亲和父亲。c.2728G<A（p.G910S）突变此前已有报道，而c.269C>G（p.P90R）是一个新突变。