Identification of phenylketonuria patient genotypes using single-gene full-length sequencing

Abstract

Abstract Background Phenylketonuria (PKU) is a common, autosomal recessive inborn error of metabolism caused by PAH gene variants. After routine genetic analysis methods were applied, approximately 5% of PKU patients were still not diagnosed with a definite genotype. Methods In this study, for the first time, we identified PKU patients with unknown genotypes via single-gene full-length sequencing. Results The detection rate of PKU genotype increased from 94.6 to 99.4%, an increase of approximately 5%. The variants c.1199 + 502A > T and 1065 + 241C > A were found at a high frequency in Chinese PKU patients. Conclusion Our study suggest that single-gene full-length sequencing is a rapid, efficient and cost-effective tool to improve the genotype detection rate of PKU patients. Moreover, we provides additional case data to support pathogenicity of deep intronic variants in PAH.

Keywords

• Phenylketonuria
• PAH
• Single-gene full-length sequencing
• Deep intronic variant