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

Hum Genomics. 2022 Jul 22;16(1):23. doi: 10.1186/s40246-022-00397-w.


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: Deep intronic variant; PAH; Phenylketonuria; Single-gene full-length sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Association Studies
  • Genotype
  • Humans
  • Mutation
  • Phenylalanine Hydroxylase* / genetics
  • Phenylketonurias* / diagnosis
  • Phenylketonurias* / genetics


  • Phenylalanine Hydroxylase