Identification of four novel mutations in the phenylalanine hydroxylase gene in patients with PKU
10.3760/cma.j.issn.1009-9158.2011.06.015
- VernacularTitle:苯丙酮尿症患儿四种苯丙氨酸羟化酶基因新突变分析
- Author:
Wuzhong YU
;
Donghui QIU
;
Jiang HE
;
Hongyun ZOU
;
Rui WANG
;
Liu YANG
- Publication Type:Journal Article
- Keywords:
Phenylketonurias;
Phenylalanine hydroxylase;
Mutation
- From:
Chinese Journal of Laboratory Medicine
2011;34(6):538-541
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the distributions of PAH gene mutation and provide guidance for gene diagnosis and prenatal diagnosis of patients with PKU in Xinjiang of China.Methods A total of 15 patients (aged from 2 to 10 years, all with blood Phe concentration over 700 μmol/L) who visited Urumqi general hospital of Lanzhou Command were clinically diagnosed as PKU and were included in this study. PCR followed by DNA sequencing was performed to analyze the promoters, all the 13 exons and their flanking introns of PAH gene in these 15 PKU patients.Results PAH gene of 15 PKU patients was amplified by PCR, and PCR products were subjected to DNA sequencing directly.Four PAH gene mutation types, including 5′- Flanking-626G > A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G>C, were identified in each of four PKU patients.Consequently reverse DNA sequencing showed G>A at -626 site, ACT deletion at -480 position in the promoter of PAH gene, an insertion at 584 site in the coding region and G>C at the border between exon 8 and intron 8 of PAH gene, respectively. After inquirying from PAH website and international PAH database (www.pahdb.mcgill.ca), these four PAH gene mutation types were verified as novel PAH gene mutations. Additionally, four patients carrying either of these four PAH gene mutation aged 3-5 years old were characterized by typical clinical phenotypes including blood Phe levels between 1 572-1 782 μmol/L, mental retardation, yellow hair and mousy odor of hair, skin and urine. Conclusions 5′-Flanking-626G>A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G > C are identified as four novel PAH gene mutations to cause PKU directly probably either by disrupting the normal 3-D structure and affecting enzymatic activity of PAH or depressing the transcription and translation of PAH gene.Together, our identification of four novel PAH gene mutations will provide important clues for future gene diagnosis and prenatal diagnosis of PKU.
