Analysis of the genotype-phenotype correlation in patients with phenylketonuria in mainland China

被引:16
作者
Li, Nana [1 ,2 ]
He, Chunhua [1 ,2 ]
Li, Jing [3 ]
Tao, Jing [1 ,2 ]
Liu, Zhen [1 ,2 ]
Zhang, Chunyan [3 ]
Yuan, Yuan [4 ]
Jiang, Hui [5 ,6 ]
Zhu, Jun [1 ,2 ]
Deng, Ying [1 ,2 ]
Guo, Yixiong [1 ,2 ]
Li, Qintong [2 ]
Yu, Ping [1 ,2 ]
Wang, Yanping [1 ,2 ]
机构
[1] Sichuan Univ, West China Univ Hosp 2, Natl Ctr Birth Defect Monitoring, Chengdu, Sichuan, Peoples R China
[2] Sichuan Univ, Minist Educ, Key Lab Birth Defects & Related Dis Women & Child, Chengdu, Sichuan, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, Lab Translat Med, Beijing, Peoples R China
[4] BGI Shenzhen, Tianjin Med Lab, BGI Tianjin, Tianjin 300308, Peoples R China
[5] BGI Shenzhen, Shenzhen 518103, Peoples R China
[6] BGI Shenzhen, China Natl GeneBank, Shenzhen 518120, Peoples R China
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
基金
中国国家自然科学基金;
关键词
PHENYLALANINE-HYDROXYLASE DEFICIENCY; MOLECULAR CHARACTERIZATION; EXPRESSION ANALYSIS; MUTATION SPECTRUM; PAH GENE; HETEROGENEITY; MECHANISM; SUBUNITS;
D O I
10.1038/s41598-018-29640-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mutations in the gene encoding phenylalanine hydroxylase (PAH) are associated with various degrees of phenylketonuria (PKU). The aim of our study was to define the genotype-phenotype correlations of mutations in the PAH gene that cause phenylketonuria (PKU) among the Chinese mainland population. Mutations in the PAH gene were analysed by next-generation sequencing, and a genotype-phenotype correlation analysis was performed in 1079 patients. Fifteen "null + null" genotypes, including four homoallelic and eleven heteroallelic genotypes, were clearly associated with classic PKU. Five functionally hemizygous (p. E280K, p. R252Q, p. E56D, p. S310F and p. T372R) and four compound heterozygous (p. T278I/p. S359L, p. R408W/p. R243Q, p. F161S/p. R243Q and p. F161S/p. R413P) genotypes were clearly associated with classic PKU. Ten functionally hemizygous genotypes, p. G257V, p. R158W, p. L255S, p. G247V, p. F161S, p. R158Q, p. V388M, p. I65T, p. I324N and p. R400K, were frequently associated with classic PKU. Three functionally hemizygous genotypes, p. P147L, p. I95del and p. F331S, and four compound heterozygous genotypes, p. G257V/p. R408Q, p. A434D/p. R413P, p. R243Q/p. A47E and p. R241C/p. G239D, were consistently correlated with mild PKU. Three functionally hemizygous genotypes, p. H107R, p. Q419R and p. F392I, and nine compound heterozygous genotypes (p. G312V/p. R241C, p. R243Q/p. V230I, p. R243Q/p. A403V, p. R243Q/p. Q419R, p. R243Q/p. R53H, p. R243Q/p. H107R, p. R241C/p. R408Q, p. R241C/p. H220P and p. R53H/p. R400K) were consistent with mild hyperphenylalaninaemia (MHP). Our study provides further support for the hypothesis that the PAH genotype is the main factor that determines the phenotype of PKU.
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页数:7
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