Qiu Xiaolong, Zhao Peiran, Luo Jinying, Li Guilin, Deng Lin, Zeng Yinglin, Xu Liangpu, Zhou Jinfu
Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Obstetrics and Gynecology Department, Fujian Maternity and Child Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Front Genet. 2023 Aug 11;14:1250568. doi: 10.3389/fgene.2023.1250568. eCollection 2023.
The estimated prevalence of tetrahydrobiopterin deficiency (BH4D) and the mutational spectrum of the causal 6-pyruvoyl-tetrahydropterin synthase () gene vary widely according to race and region. This study assessed the prevalence and genetic characteristics of BH4D in Fujian Province, southeastern China. A total of 3,204,067 newborns were screened between 2012 and 2022 based on the phenylalanine level and the phenylalanine/tyrosine ratio in dried blood spots. Differential diagnosis was determined by the urine purine spectrum, dihydropteridine reductase activity in red blood cells, and genetic testing. The mutation spectrum and genotypes were determined by next-generation sequencing. A total of 189 newborns were diagnosed with hyperphenylalaninemia (HPA) over the study period, including 159 with phenylalanine hydroxylase deficiency and 30 with BH4D. Therefore, the prevalence of BH4D in Fujian was 9.36 per 1,000,000 live births (30/3,204,067) and the proportion of BH4D among patients with HPA was 15.87% (30/189). A total of 58 alleles were identified in the 29 patients with PTS deficiency (PTPSD), and those alleles were composed of 10 different variants, including eight missense variants and two splice-site variants. The most prevalent variants were c.155A>G, p.Asn52Ser (44.83%); c.259C>T, p.Pro87Ser (39.66%); and c.84-291A>G, p.Tyr27Argfs*8 (3.45%). The predominant genotype was c [155A>G]; [259C>T] (11/29, 37.93%). The prevalence of BH4D and the spectrum of associated mutations were successfully determined for the first time in Fujian Province, southeastern China. Since the mutation spectrum of is region-specific, such data will facilitate molecular diagnosis and genetic counseling in PTPSD cases.
四氢生物蝶呤缺乏症（BH4D）的估计患病率以及致病的6-丙酮酰四氢蝶呤合成酶（PTPS）基因的突变谱因种族和地区而异。本研究评估了中国东南部福建省BH4D的患病率和遗传特征。2012年至2022年期间，基于干血斑中的苯丙氨酸水平和苯丙氨酸/酪氨酸比值，对总共3,204,067名新生儿进行了筛查。通过尿嘌呤谱、红细胞中二氢蝶呤还原酶活性和基因检测进行鉴别诊断。通过下一代测序确定PTPS突变谱和基因型。在研究期间，共有189名新生儿被诊断为高苯丙氨酸血症（HPA），其中159名患有苯丙氨酸羟化酶缺乏症，30名患有BH4D。因此，福建地区BH4D的患病率为每1,000,000例活产9.36例（30/3,204,067），在HPA患者中BH4D的比例为15.87%（30/189）。在29例PTPS缺乏症（PTPSD）患者中总共鉴定出58个PTPS等位基因，这些等位基因由10种不同的变异组成，包括8种错义变异和2种剪接位点变异。最常见的变异是c.155A>G，p.Asn52Ser（44.83%）；c.259C>T，p.Pro87Ser（39.66%）；和c.84-291A>G，p.Tyr27Argfs*8（3.45%）。主要基因型是c.[155A>G]；[259C>T]（11/29，37.93%）。首次成功确定了中国东南部福建省BH4D的患病率和相关PTPS突变谱。由于PTPS的突变谱具有区域特异性，此类数据将有助于PTPSD病例的分子诊断和遗传咨询。
