The Department of Laboratory Medicine, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Neonatal Screening Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Hum Genomics. 2022 Jul 22;16(1):23. doi: 10.1186/s40246-022-00397-w.
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.
In this study, for the first time, we identified PKU patients with unknown genotypes via single-gene full-length sequencing.
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.
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.
苯丙酮尿症（PKU）是一种常见的常染色体隐性遗传代谢缺陷病，由 PAH 基因突变引起。在应用常规基因分析方法后，仍有约 5%的 PKU 患者未明确基因型。
本研究首次通过单基因全长测序鉴定了不明基因型的 PKU 患者。
PKU 基因型的检出率从 94.6%提高到 99.4%，提高了约 5%。在中国 PKU 患者中，c.1199 + 502A > T 和 1065 + 241C > A 这两种变体的出现频率较高。
本研究表明，单基因全长测序是一种快速、高效、经济有效的工具，可提高 PKU 患者的基因型检出率。此外，本研究还提供了额外的病例数据，支持 PAH 基因中深内含子变异的致病性。
