Non-invasive prenatal testing of pregnancies at risk for phenylketonuria
| Autor: | Huikun Duan, Zhenhua Zhao, Xiangdong Kong, Yiqian Liu, David S. Cram, Ning Liu, Mengnan Xu, Zhifeng Li, Yin Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Phenylalanine hydroxylase Prenatal diagnosis Compound heterozygosity 03 medical and health sciences symbols.namesake 0302 clinical medicine Phenylketonurias Prenatal Diagnosis 030225 pediatrics Genotype medicine Humans Amniocyte Multiplex 030212 general & internal medicine Phenylketonuria (PKU) Retrospective Studies Sanger sequencing Hematologic Tests biology Obstetrics business.industry Phenylalanine Hydroxylase Obstetrics and Gynecology General Medicine medicine.disease Pediatrics Perinatology and Child Health biology.protein symbols business |
| Zdroj: | Archives of Disease in Childhood - Fetal and Neonatal Edition. 104:F24-F29 |
| ISSN: | 1468-2052 1359-2998 |
| DOI: | 10.1136/archdischild-2017-313929 |
| Popis: | BackgroundPhenylketonuria (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).MethodsA 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.ResultsBenchmarking 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.ConclusionsThe 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. |
| Databáze: | OpenAIRE |
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