Zhang Ting, Yang Jianbin, Yin Xiaoshan, Yu Ping, Mooney Robert, Huang Xinwen, Qi Ming
Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, 57 Zhugan Xiang, Hangzhou 310003, China.
School of Medicine, Hangzhou Normal University, 16 Xuelin Street, Hangzhou 311121, China.
Clin Chim Acta. 2017 Mar;466:68-71. doi: 10.1016/j.cca.2017.01.011. Epub 2017 Jan 12.
Argininemia is a rare autosomal recessive genetic disorder caused by deficiency of arginase Ι, resulting from mutations in the ARG1 gene. Few genetic studies of ARG1 mutations in Chinese patients have been reported. In this study, two argininemia patients were initially diagnosed by tandem mass spectrometry in newborn screening. Mutation analysis of the ARG1 gene was performed by direct sequencing. Three novel mutations were identified and in silico methods were used to predict the impact of these mutations on the activity of enzyme. Two missense mutations, p.D100N and p.R71T, in Patient-1 were predicted to lower the stability of arginase Ι by analysis of 3D crystal structure, while two nonsense mutations, p.G12X and p.E42X, in Patient-2 were predicted to lead to truncated protein. Neonatal screening combined with genetic analysis is important for timely diagnosis and initiation of interventions of a potential genetic metabolic disease such as argininemia.
精氨酸血症是一种罕见的常染色体隐性遗传疾病，由精氨酸酶Ⅰ缺乏引起，是由ARG1基因突变所致。关于中国患者中ARG1基因突变的遗传学研究报道较少。在本研究中，两名精氨酸血症患者最初在新生儿筛查中通过串联质谱法被诊断出来。采用直接测序法对ARG1基因进行突变分析。鉴定出三个新的突变，并使用计算机模拟方法预测这些突变对酶活性的影响。通过对三维晶体结构的分析，预测患者1中的两个错义突变p.D100N和p.R71T会降低精氨酸酶Ⅰ的稳定性，而患者2中的两个无义突变p.G12X和p.E42X预计会导致截短蛋白的产生。新生儿筛查与基因分析相结合对于及时诊断和启动对潜在的遗传代谢疾病（如精氨酸血症）的干预措施非常重要。
