一例尿刊酸酶缺乏症的临床特点及基因突变分析

Analysis of clinical data and genetic mutations in one Chinese patients with urocanase deficiency

目的探讨尿刊酸酶缺乏症的临床特征及基因突变特点,为临床诊治提供思路。方法报道1例UROC1基因突变致尿刊酸酶缺乏症患者的临床资料和基因检测结果,并进行文献复习。结果全外显子测序结果显示患者携带UROC1基因c.1291C>G(p.P431A)与c.1803C>G(p.1601M)复合杂合突变,父亲携带c.1291C>G(p.P431A)突变,母亲携带c.1803C>G(p.1601M)突变。经检索ExAC、gnomAD数据库及千人基因组数据库,c.1803C>G(p.1601M)突变为未报道过的新突变,c.1291C>G(p.P431A)突变在人群中频率为0.000012。生物学信息分析软件预测蛋白功能,提示能产生有害影响。结论随着精准医学的推广,全外显子组测序技术帮助明确了许多遗传病的致病原因,增加了罕见病的临床症状类型。本文报道的UROC1基因的c.1291C>G(p.P431A)与c.1803C>G(p.1601M)均为首次发现的突变,可能会引起尿刊酸酶的结构功能异常,从而导致尿刊酸酶缺乏症。

Objective To explore the clinical characteristics and gene mutation features of urocanase deficiency to provide ideas for clinical diagnosis and treatment.Methods The clinical information and whole exome sequencing result of an urocanase deficiency patient that carried mutations in UROC1 gene was reported and the relative literature was reviewed.Results Analysis showed that the patient carried compound heterozygous mutations c.1291C>G and c.1803C>G of the UROC1 gene,which derived his father and mother,respectively.c.1803C>G(p.1601M)mutations was verified as novel through the retrieval of ExAC,gnomAD and 1000 genome databases,c.1291C>G(p.P431A).The mutation frequency in the population is 0.000012.Bioinformatic analysis suggested that the mutations can affect protein function.Conclusion With the promotion of precision medicine,whole exome sequencing technology has helped to clarify the pathogenic causes of many genetic diseases.Increased the clinical symptom types of rare diseases.c.1291C>G(p.P431A)and c.1803C>G(p.1601M)both the first discovered mutation,novel pathogenic mutations in UROC1 gene that could cause abnormality in structure and function in urocanase.These mutations may cause urocanase deficiency.