摘要
目的探讨1例植物固醇血症家系及其致病基因突变。方法对1例诊断为植物固醇血症的患者及其家系成员进行家系调查;通过PCR扩增先证者及其家系成员基因组DNA中ABCG5及ABCG8基因的所有外显子及其侧翼序列,采用Sanger测序法对PCR产物进行基因测序;采用Polyphen2及Mutation Taster生物信息学软件预测突变的致病性。结果Sanger测序法发现先症者及家系成员中存在多个基因突变,其中ABCG5基因发现3个突变,分别为外显子1 c.64C>T(p.Q22X)杂合无义突变、外显子10 c.1336C>T(p.R446X)杂合无义突变、外显子13 c.1810C>G(p.Q604E)杂合错义突变;ABCG8基因发现4个突变,分别为(ATG前)-19T>G纯合突变、外显子2 c.161A>G(p.Y54C)纯合错义突变、外显子13 c.1895T>C(p.V632A)纯合错义突变、外显子4和5间的内含子g.12902T>C纯合突变。Polyphen2及Mutation Taster软件预测ABCG5基因中c.64C>T及c.1336C>T为致病突变,其他基因突变均为非致病性的多态性位点。结论ABCG5基因c.64C>T及c.1336C>T复杂杂合突变是该植物固醇血症家系的基因发病机制。
Objective To explore the mutation of pathogenic genes in a sitosterolemia pedigree. Methods A patient diagnosed as phytosterolemia and his family members were received pedigree survey. All the exons and the flanking sequences of ABCG5 and ABCG8 genes in thegenomic DNA were amplified by PCR and the sequencing for PCR products were performed by Sanger method. Pathogenicity of gene mutations was predicted by using online bioinformatic prediction software Polyphen-2 and Mutation Taster. Results Sanger sequencing revealed multiple mutations in the proband and his family members. Three mutations, were found in ABCG5 gene, i.e., c.64 C>T(p.Q22 X) heterozygous nonsense mutation in exon 1, c.1336 C>T(p.R446 X) heterozygous nonsense mutation in exon 10 and c.1810 C>G(p.Q604 E) heterozygous missense mutation in exon 13. Four mutations were found in ABCG8 gene, i.e.,-19 T>G pre-ATG homozygous mutation, c.161 A>G(p.Y54 C) homozygous missense mutation in exon 2, c.1895 T>C(p.V632 A) homozygous missense mutation in exon 13 and g.12902 T>C homozygous mutation in the intron between exon 4 and 5. Polyphen-2 and Mutation Taster software predicted that c.64 C>T and c.1336 C>T in the ABCG5 gene were pathogenic mutations, but other gene mutations were non-pathogenic polymorphic sites. Conclusion The compound c.64 C>T and c.1336 C>T heterozygous mutations in ABCG5 gene should be the genetic pathogenesis for this sitosterolemia pedigree.
作者
叶文灿
徐静
李振江
饶燕飞
宋渊
费妍
杨桂玲
汤爱平
YE Wencan;XU Jing;LI Zhenjiang;Rao Yanfei;SONG Yuan;FEI Yan;YANG Guiling;TANG Aiping(The Second Affiliated Hospital of Nanchang University,Department of Hematology&Jiangxi Province Key Laboratory of Hematology,Nanchang 330006,Jiangxi,China;The Second Affiliated Hospital of Nanchang University,Department of Clinical Laboratory,Nanchang 330006,Jiangxi,China)
出处
《临床检验杂志》
CAS
2020年第7期553-557,共5页
Chinese Journal of Clinical Laboratory Science
基金
国家自然科学基金(81460029)
江西省“5511”科技创新人才项目(20171BCB18003)。
