Gansu Province Medical Genetics Center,Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, China.
National Research Institute for Family Planning , National Human Genetic Resources Center, Beijing, China.
Hum Genomics. 2023 Apr 25;17(1):36. doi: 10.1186/s40246-023-00475-7.
Phenylketonuria (PKU) is a common, congenital, autosomal recessive, metabolic disorder caused by Phenylalanine hydroxylase (PAH) variants.
967 PKU patients from Gansu, China were genotyped by Sanger sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing. We analyzed the variants of PAH exons, their flanking sequences, and introns.
The detection of deep intronic variants in PAH gene can significantly improve the genetic diagnostic rate of PKU. The distribution of PAH variants among PKU subtypes may be related to the unique genetic background in Gansu, China.
The identification of PAH hotspot variants will aid the development of large-scale neonatal genetic screening for PKU. The five new PAH variants found in this study further expand the spectrum of PAH variants. Genotype-phenotype correlation analysis may help predict the prognosis of PKU patients and enable precise treatment regimens to be developed.
苯丙酮尿症（PKU）是一种常见的先天性常染色体隐性遗传代谢疾病，由苯丙氨酸羟化酶（PAH）变异引起。
对来自中国甘肃的 967 例 PKU 患者进行 Sanger 测序、多重连接依赖性探针扩增和全外显子组测序。我们分析了 PAH 外显子及其侧翼序列和内含子的变异。
在 PAH 基因中检测到深内含子变异可显著提高 PKU 的遗传诊断率。PKU 亚型中 PAH 变异的分布可能与中国甘肃独特的遗传背景有关。
PAH 热点变异的鉴定将有助于开展大规模新生儿 PKU 遗传筛查。本研究发现的 5 种新的 PAH 变异进一步扩展了 PAH 变异谱。基因型-表型相关性分析有助于预测 PKU 患者的预后，并制定精准的治疗方案。
