肝豆状核变性的ATP7B基因变异分析及产前诊断

doi:10.6040/j.issn.1671-7554.0.2021.0721

摘要/Abstract

摘要： 目的对肝豆状核变性家系行遗传学分析,明确该家系的遗传病因。方法对家系中肝豆状核变性先证者行全外显子测序分析,Sanger测序对先证者及父母筛出的可疑致病变异进行验证,该父母孕育的二胎胎儿行羊水穿刺,行产前基因诊断。结果发现先证者存在ATP7B基因复合杂合变异,即NM_000053.3:c.2333G>T(p.Arg778Leu)错义杂合变异和NM_000053.3:c.208delC(p.Gln70Ser fs*4)缺失移码变异;其中,c.2333G>T错义杂合变异来源于父亲,为数据库已经报道的变异;c.208delC缺失移码变异来源于母亲,暂未见报道。先证者母亲孕20周,行胎儿产前基因诊断,发现胎儿仅携带来源于母亲的ATP7B基因c.208delC移码杂合变异,c.2333位点为野生型,胎儿和先证者基因型不同,预测胎儿不会出现和先证者一样的肝豆状核变性的临床表型。结论该肝豆状核变性先证者临床表型异常是由ATP7B基因复合杂合变异所致,为生二胎先证者父母的遗传咨询和产前诊断提供了理论依据。

关键词: 肝豆状核变性, 基因变异, ATP7B基因, Sanger测序

Abstract: Objective Genetic testing and prenatal diagnosis were used to identify the pathogenic gene variation of Wilson disease in a family. Methods Whole exon sequencing was used to analyze the proband with hepatolenticular degeneration in the family and Sanger sequencing was used to identify the suspected pathogenic variation screened by the proband and his parents. Amniocentesis was performed on the second fetus for prenatal genetic diagnosis. Results It was found that the proband had complex heterozygous variation of ATP7B gene. The missense variation was named NM_000053.3:c.2333G>T(p.Arg778Leu)from his father and the deletion variation was named NM_000053.3:c.208delC(p.Gln70Ser fs*4)from his mother. The missense variation c.2333G>T had been reported and the deletion variation c.208delC had been not reported. The proband's mother underwent prenatal genetic diagnosis at 20 weeks of pregnancy. It was found that the fetus only carried the c.208delC deletion variation from the mother and the c.2333 locus was wild type. The fetus and the proband had different genotypes which predicted that the fetus would not have the same clinical manifestations of hepatolenticular degeneration as the proband. Conclusion The abnormal clinical phenotype of the Wilson disease proband is caused by the complex heterozygous variation of ATP7B gene. It provides the basis for the genetic counseling and prenatal diagnosis for parents who will give birth to a second child.

Key words: Wilson disease, Gene variation, ATP7B gene, Sanger sequencing

中图分类号:

R574

王婧,刘小转,许芳芳. 肝豆状核变性的ATP7B基因变异分析及产前诊断[J]. 山东大学学报 (医学版), 2022, 60(2): 32-36.

WANG Jing, LIU Xiaozhuan, XU Fangfang. Genetic testing and prenatal diagnosis for a pedigree affected with ATP7B gene variation in Wilson disease[J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 32-36.

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