Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria in Shaanxi, China

Background: This study aims to investigate the spectrum and frequency of phenylalanine hydroxylase (PAH) gene mutations and the power to prenatally diagnose phenylketonuria (PKU) patients in Shaanxi, China. Methods: Polymerase chain reaction (PCR) and DNA sequencing analyses were performed to examine the PAH gene in 33 PKU patients and seven amniotic fluid samples. Thirty-four pathogenic variants were indicated in all 63 alleles, in which two probands carried three variants. Results: Pedigree analysis suggested that the [c.158G>A([p.R53H)][IVS7+2T>A] mutation was located at the same chromatid. However, there was a controversial viewpoint that thought the c.158G>A(p.R53H) variant was a polymorphism in the Chinese. We also found one novel indel mutation and identified the c.59_60delAGinsCC mutation of the PAH gene for the very first time. The spectrum of the PAH mutations in Shaanxi Province were similar to that among China's population. Based on the results of PAH gene analysis, we further performed prenatal genetic diagnoses for seven PKU families. All foetuses were definitively diagnosed, and their parents were provided with genetic counselling. Conclusions: PAH gene analysis is a crucial method for PKU diagnosis and prenatal genetic prognosis, even though many uncommon mutations would affect the analysis and diagnosis of genetic abnormalities.