Department of Basic Medicine, Hebei Medical University, 361 Zhongshan East Road, Chang'an District, Shijiazhuang, 050011, Hebei Province, China.
Department of Public Health, Hebei Medical University, 361 Zhongshan East Road, Chang'an District, Shijiazhuang, 050011, Hebei Province, China.
Orphanet J Rare Dis. 2024 Sep 12;19(1):337. doi: 10.1186/s13023-024-03287-7.
Porphyria is a group of rare metabolic disorders caused by mutations in the genes encoding crucial enzymes in the heme biosynthetic pathway. However, the lack of comprehensive genetic analysis of porphyria patients in the Chinese population makes identifying and diagnosing carriers of the condition challenging. Using the ChinaMAP database, we determined the frequencies of P/LP porphyria-associated gene variants according to the ACMG guidelines. We also calculated the carrier rates and prevalence of each type of porphyria in the Chinese population under Hardy-Weinberg equilibrium. Compared with the variants in the gnomAD database, the genetic spectrum of porphyria-related P/LP variants in the Chinese population is distinct. In the ChinaMAP database, we identified 23 variants. We estimated the carrier rates for autosomal dominant porphyrias (AIP, HCP, VP, PCT) in the Chinese population to be 1/1059, 1/1513, 1/10588, and 1/1765, respectively. For autosomal recessive porphyrias (ADP, EPP, HEP, CEP), the estimated carrier rates were 1/5294, 1/2117, 1/1765, and 1/2647, respectively, with predicted prevalence rates of 8.92 × 10, 7.51 × 10, 8.02 × 10, and 3.57 × 10, respectively. Notably, 12 of the variants we identified were unique to the Chinese population. The predicted prevalence rate of EPP was the highest among the various types of porphyria in the Chinese population, while the others were moderate to low. This is the first comprehensive genetic study on porphyria in the Chinese population. Clarifying the genetic characteristics of various porphyria types among the Chinese population provides scientifically sound reference data for both research and genetic screening to identify porphyria carriers.
卟啉病是一组罕见的代谢紊乱疾病，由血红素生物合成途径中关键酶的基因突变引起。然而，由于中国人群中卟啉病患者缺乏全面的遗传分析，因此识别和诊断该疾病的携带者具有挑战性。本研究使用中国罕见病基因组联盟（ChinaMAP）数据库，根据 ACMG 指南确定了与卟啉病相关的 P/LP 基因变异的频率。我们还根据 Hardy-Weinberg 平衡计算了每种类型卟啉病在中国人群中的携带者频率和患病率。与 gnomAD 数据库中的变异相比，中国人群中与卟啉病相关的 P/LP 变异的遗传谱是不同的。在 ChinaMAP 数据库中，我们鉴定了 23 个变异。我们估计中国人群中常染色体显性遗传卟啉病（AIP、HCP、VP、PCT）的携带者频率分别为 1/1059、1/1513、1/10588 和 1/1765。对于常染色体隐性遗传卟啉病（ADP、EPP、HEP、CEP），预计携带者频率分别为 1/5294、1/2117、1/1765 和 1/2647，预测患病率分别为 8.92×10、7.51×10、8.02×10 和 3.57×10。值得注意的是，我们鉴定的 12 个变异是中国人群所特有的。在中国人群中，EPP 的预测患病率是各种类型卟啉病中最高的，而其他类型的患病率则适中或较低。这是中国人群中卟啉病的首次全面遗传研究。阐明中国人群中各种卟啉病类型的遗传特征，为研究和遗传筛查识别卟啉病携带者提供了科学依据。
