Author:
Zhang Chuan,Zhang Pei,Yan Yousheng,Zhou Bingbo,Wang Yupei,Tian Xinyuan,Hao Shengju,Ma Panpan,Zheng Lei,Zhang Qinghua,Hui Ling,Wang Yan,Cao Zongfu,Ma Xu
Abstract
Abstract
Background
Phenylketonuria (PKU) is a common, congenital, autosomal recessive, metabolic disorder caused by Phenylalanine hydroxylase (PAH) variants.
Methods
967 PKU patients from Gansu, China were genotyped by Sanger sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing. We analyzed the variants of PAH exons, their flanking sequences, and introns.
Results
The detection of deep intronic variants in PAH gene can significantly improve the genetic diagnostic rate of PKU. The distribution of PAH variants among PKU subtypes may be related to the unique genetic background in Gansu, China.
Conclusion
The identification of PAH hotspot variants will aid the development of large-scale neonatal genetic screening for PKU. The five new PAH variants found in this study further expand the spectrum of PAH variants. Genotype–phenotype correlation analysis may help predict the prognosis of PKU patients and enable precise treatment regimens to be developed.
Funder
National Key Research and Development Program of China
Lanzhou Science and Technology Plan Project
National Population and Reproductive Health Science Data Center
National Science and Technology Resource Sharing Service Platform Project
Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases
Gansu Natural Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
Drug Discovery,Genetics,Molecular Biology,Molecular Medicine