与嘌呤代谢相关的单基因肾结石病的研究进展

Advances of monogenic kidney stone diseases associated with purine metabolism

一些肾结石病是由单基因病所致,其中与嘌呤代谢相关的单基因病主要包括腺嘌呤磷酸核糖基转移酶(APRT)缺乏症、次黄嘌呤-鸟嘌呤-磷酸核糖基转移酶(HPRT)缺乏症、遗传性黄嘌呤尿症(HX)以及由PRS1、SLC22A12、SLC2A9和ABCG2等基因突变所致病症。这类疾病可导致嘌呤和尿酸代谢异常,进而形成2,8-二羟基腺嘌呤结石、尿酸结石或黄嘌呤结石等。此类疾病临床罕见,不同类型的与嘌呤代谢相关的单基因肾结石病的基因型和表型有其各自特点,且不被广泛认知。目前药物治疗是此类疾病的主要治疗方法。随着基因诊断和治疗技术的进步,不断有新的致病基因和位点被发现,同时随着CRISPR/Cas9等基因编辑技术的逐步应用,与嘌呤代谢相关的单基因肾结石病在未来有望从根本上得到治愈。

Some kidney stones are caused by single gene mutations,and monogenic kidney stone diseases associated with purine metabolic disorder mainly including adenine phosphoribosyltransferase(APRT)deficiency,hypoxanthine-guanine phosphoribosyltransferase(HPRT)deficiency,hereditary xanthinuria(HX),and some diseases caused by gene mutations such as PRS1,SLC22A12,SLC2A9 and ABCG2.Such diseases can lead to abnormal metabolism of purine and uric acid,and then form 2,8-dihydroxyadenine stones,uric acid stones or xanthine stones.This kind of diseases are rare,the genotype and phenotype of different types of monogenic diseases related to purine metabolism have their own characteristics and are not widely recognized.At present,the main treatment is medical therapy.Gene sequencing will make the diagnosis and find more disease-related genes or mutations.Gene editing,such as CRISPR/Cas9 technology,makes it possible to cure monogenic kidney stone diseases associated with purine metabolism disorder in the future.