Ya-fen Chen1, Hai-tao Jia2, Zhong-hai Chen3, Jia-ping Song4, Yu Liang5, Jing-jing Pei6, Zhi-jun Wu7, Jing Wang8, Ya-li Qiu9, Gang Liu10, Dong-mei Sun11, Xin-ye Jiang12. 1. Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. chenyafen999@126.com. 2. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. jiahaitao@genomics.cn. 3. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. chenzhonghai@genomics.cn. 4. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. songjiaping@genomics.cn. 5. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. liangyu@genomics.cn. 6. Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. pjj2226@aliyun.com. 7. Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. wzj3045@wxfuyou.com. 8. Department of Children Health Care, Suqian Maternal and Child Health Hospital, No. 9 Ping-An Road, Suqian, Jiangsu Province, China. sqwj9187@126.com. 9. Department of Children Health Care, Suqian Maternal and Child Health Hospital, No. 9 Ping-An Road, Suqian, Jiangsu Province, China. 18082308992@189.com. 10. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. liugang@genomics.cn. 11. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China. sundongmei@genomics.cn. 12. Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China. fyjxy2110@163.com.
Abstract
UNLABELLED: 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. CONCLUSION: 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. WHAT IS KNOWN: • 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.
UNLABELLED: 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. CONCLUSION: 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. WHAT IS KNOWN: • 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: Roberta Trunzo; Rosa Santacroce; Giovanna D'Andrea; Vittoria Longo; Giuseppe De Girolamo; Claudia Dimatteo; Angelica Leccese; Vincenza Lillo; Francesco Papadia; Maurizio Margaglione Journal: Clin Biochem Date: 2013-06-18 Impact factor: 3.281
Authors: P Guldberg; V Romano; N Ceratto; P Bosco; M Ciuna; A Indelicato; F Mollica; C Meli; M Giovannini; E Riva Journal: Hum Mol Genet Date: 1993-10 Impact factor: 6.150
Authors: Marcel R Zurflüh; Johannes Zschocke; Martin Lindner; François Feillet; Céline Chery; Alberto Burlina; Raymond C Stevens; Beat Thöny; Nenad Blau Journal: Hum Mutat Date: 2008-01 Impact factor: 4.878
Authors: Ting Wang; Jun Ma; Qin Zhang; Ang Gao; Qi Wang; Hong Li; Jingjing Xiang; Benjing Wang Journal: Front Genet Date: 2019-10-29 Impact factor: 4.599