Mutation analysis in exon 11 of the PAH gene in phenylketonuria patients in five provinces and regions of Northwest China

Abstract

Objective To investigate the mutation characteristics in exon 11 of the phenylalanine hydroxylase (PAH) gene in phenylketonuria (PKU) patients in five provinces and regions of Northwest China, and then to provide basic information for genetic counseling and prenatal diagnosis. Methods Mutations of the PAH gene were detected in promoter, exons 1-13 with flanking introns of PAH gene by PCR and DNA sequencing in 276 families with PKU. Results ①Forty-seven mutant alleles in exon 11 of PAH gene were identified in 552 chromsomes from 276 PKU patients, with relative frequency of 8.5%. A total of 7 different mutations were detected, including 5 missense(71.4%), 1 nonsense(14.3%) and 1splice-site(14.3%). Three missense mutations including Y356X, V399V and R400T were identified with relative higher frequencies of 3.8%, 2.2% and 1.1%, respectively. ②The frequency of mutation alleles in exon 11 of PAH gene in Gansu, Qinghai, Xinjiang, Ningxia and Shaanxi were 19.0%, 13.3%, 7.4%, 6.0% and 4.8%, respectively. Furthermore, the Y356X mutation was novel in Xinjiang (4.1%), Ningxia (3.3%) and Qinghai (7.1%). The novel mutations in Shaanxi and Gansu were R400T (2.4%) and V399V (12.1%), respectively. ③Y356X and V399V were the most prevalent mutation form in Northwest and most provinces of China. The frequencies of Y356X and V399V mutations in Northwest were significantly lower than those of the most provinces such as Neimenggu, Beijing, Henan, Hebei and Tianjin, etc (P<0.05). In addition, the frequency of V388M in Northwest were significantly lower than those of Korea, Spain and Portugal (P<0.05). Reviewing literature at home and abroad, it is found that F392I has not been reported in southern China and thus, the mutation of F392I is likely a new type of PAH gene mutation in Northwest China. Conclusion ①Y356X and V399V are two common mutations in exon 11 of PAH gene in PKU patients from Northwest China different from that Korea and Japan where Y356X and V388M mutations where dominant. The regions with higher frequency of Y356X and V399V mutations were Neimenggu and Tianjin provinces of China. ②According to the research, the types and characteristics of the gene mutation in exon 11 of PAH gene in five provinces and regions of Northwest China are different from other areas in China. The gene mutation in this area shows their diversity and complexity as well as significant ethnic uniqueness. Key words: Phenylketonuria; Phenylalanine hydroxylase; Mutation