产前诊断
医学
苯丙氨酸羟化酶
突变
桑格测序
杂合子优势
怀孕
基因突变
基因检测
复合杂合度
载波测试
产前筛查
基因型
苯丙酮尿症
胎儿
儿科
遗传学
遗传咨询
基因
绒毛取样
生物
内科学
苯丙氨酸
氨基酸
作者
Huikun Duan,Ning Liu,Zhen-Hua Zhao,Yiqian Liu,Yin Wang,Zhifeng Li,Mengnan Xu,David S. Cram,Xiangdong Kong
出处
期刊:Archives of Disease in Childhood-fetal and Neonatal Edition
[BMJ]
日期:2019-01-01
卷期号:104 (1): F24-F29
被引量:18
标识
DOI:10.1136/archdischild-2017-313929
摘要
Background Phenylketonuria (PKU) is a common metabolic disorder caused predominately by mutations in the phenylalanine hydroxylase ( PAH ) gene. The aim of the study was to design and validate the performance of a non-invasive prenatal test (NIPT) for PKU using circulating single molecule amplification and resequencing technology (cSMART). Methods A total of 18 couples at genetic risk for having a child with PKU were recruited to the study. Gold standard invasive prenatal diagnosis (IPD) was performed on amniocyte or villus cell DNA by Sanger sequencing, targeting the known parental PAH mutations. Retrospectively, NIPT was also performed on stored maternal plasma samples from the 18 pregnancies by a multiplex cSMART assay designed to target all known DNA variants in the PAH gene. Results Benchmarking against IPD results, NIPT correctly genotyped all fetuses, including six compound heterozygotes with PKU, four normal non-carriers of PKU and eight heterozygote carriers of PKU comprising five cases of a maternally inherited mutation and three cases of a paternally inherited mutation. Conclusions The NIPT cSMART PKU assay was highly sensitive and specific for mutation detection and correct assignment of fetal genotypes. Based on comprehensive mutation coverage across the PAH gene, the assay may initially have clinical utility as a pregnancy screening test for high-risk carrier couples.
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