title: Mutational spectrum of phenylketonuria in Jiangsu province.
abstract: Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. We systematically investigated all 13 exons of the PAH gene and their flanking introns in 31 unrelated patients and their parents using next-generation sequencing (NGS). A total of 33 different variants were identified in 58 of 62 mutant PAH alleles. The prevalent variants with a relative frequency of 5 % or more were c.721C > T, c.1068C > A, c.611A > G, c.1197A > T, c.728G > A, c.331C > T, and c.442-1G > A. One novel variant was identified in this study-c.699C > G. We studied genotype-phenotype correlations using the Guldberg arbitrary value (AV) system, which revealed a consistency rate of 38 % (8/21) among the 21 predicted phenotypes. The genotype-based prediction of BH4 responsiveness was also evaluated, and 14 patients (45.2 %) were predicted to be BH4 responsive.
  
  
  CONCLUSIONS
  This study presents the spectrum of PAH variants in Jiangsu province. The information obtained from the genotype-based prediction of BH4 responsiveness might be used for the rational selection of candidates for BH4 testing.
  
  
  BACKGROUND
  • Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. • The spectrum of PAH variants in different Chinese populations has been reported. What is new: • This is the first report on the spectrum of PAH variants in Jiangsu province. • This study identified one novel PAH variant-c.699C>G-and and tries to show a genotype-phenotype relationship also regarding BH4-responsiveness.
authors.affiliation: Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. chenyafen999@126.com.
authors.forename: Ya-fen
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. jiahaitao@genomics.cn.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Jia
authors.affiliation: Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. chenzhonghai@genomics.cn.
authors.forename: Zhong-hai
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. songjiaping@genomics.cn.
authors.forename: Jia-ping
authors.initials: JP
authors.lastname: Song
authors.affiliation: Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. liangyu@genomics.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. pjj2226@aliyun.com.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Pei
authors.affiliation: Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. wzj3045@wxfuyou.com.
authors.forename: Zhi-jun
authors.initials: ZJ
authors.lastname: Wu
authors.affiliation: Department of Children Health Care, Suqian Maternal and Child Health Hospital, No. 9 Ping-An Road, Suqian, Jiangsu Province, China. sqwj9187@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Children Health Care, Suqian Maternal and Child Health Hospital, No. 9 Ping-An Road, Suqian, Jiangsu Province, China. 18082308992@189.com.
authors.forename: Ya-li
authors.initials: YL
authors.lastname: Qiu
authors.affiliation: Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. liugang@genomics.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. sundongmei@genomics.cn.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Sun
authors.affiliation: Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. fyjxy2110@163.com.
authors.forename: Xin-ye
authors.initials: XY
authors.lastname: Jiang
mesh_terms: D000483:Alleles; D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics* / Q000378:metabolism; D010661:Phenylketonurias / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D012189:Retrospective Studies
chemical_list: D004247:DNA; D010651:Phenylalanine Hydroxylase
keywords: BH4 responsiveness; Genotype–phenotype correlation; Phenylalanine hydroxylase; Phenylketonuria