Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi, China

Abstract

The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH) gene was investigated in 59 children with phenylketonuria (PKU) and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, whereas EX6-96A > G accounted for 10.2% mutation of alleles in exon 6. R243Q had the highest incidence in exon 7 (12.7%), followed by Ivs7 + 2 T > A (5.1%) and T278I (2.5%). G247V, R252Q, L255S, R261Q and E280K accounted for 0.8% while Y356X and V399V accounted for 5.9% and 5.1%, respectively, in exon 11. R413P and A434D accounted for 5.9% and 2.5%, respectively, in exon 12. Seventy-two variant alleles accounted for the 16 mutations observed here. The mutation characteristics and distributions demonstrated that EX6-96A > G and R243Q were the hot regions for mutations in the PAH gene in Shanxi patients with PKU.

Mutation Spectrum of Six Genes in Chinese Phenylketonuria Patients Obtained through Next-Generation Sequencing

“…Using this dataset, we identified 23 known variants in the PAH gene that included 21 mutations from the core families and seven mutations from the non-core families (Table S5). Consistent with previous PKU analyses, several of the most prevalent mutations discovered in our analysis, R243Q, R241C, Y356X, V399V and R413P (Table 1), matched the predominant type of PKU-associated mutation found in the Asian population [1], [7]. These results suggest that these mutations are not only found in northern China but also in the central Chinese population.…”

Mutational spectrum of phenylketonuria in Jiangsu province

“…A study in the Chinese Han population did not find significant differences in the common variants between the southern and northern populations, with the exception of the R413P variant [18]; however, the analysis of the variants in northern China focused on genotype-phenotype correlations [12]. Other studies have described PAH gene variants in several provinces including Xinjiang and Shanxi [15,17] (Fig. 1).…”

Noninvasive fetal genotyping in pregnancies at risk for PKU using a comprehensive quantitative cSMART assay for PAH gene mutations: a clinical feasibility study

“…We propose that the current version of our assay could be used as a first‐tier screening test for high‐risk pregnancies where both partners are known carriers. The test would also have useful clinical utility in regions where the carrier rates for PKU are high and where DNA testing is not widely available, particularly in the northern provinces of China, and in countries such as Turkey, where the incidence of PKU remains very high. Potentially all pregnancies in these regions could be tested without the need for costly family DNA studies to identify those at risk for PKU, with appropriate IPD follow up to confirm any affected pregnancies.…”