title: Three novel mutations of ARG1 identified in Chinese patients with argininemia detected by newborn screening.
abstract: 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.
authors.affiliation: Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, 57 Zhugan Xiang, Hangzhou 310003, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, 57 Zhugan Xiang, Hangzhou 310003, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Medicine, Hangzhou Normal University, 16 Xuelin Street, Hangzhou 311121, China.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, 588 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Mooney
authors.affiliation: Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, 57 Zhugan Xiang, Hangzhou 310003, China. Electronic address: xinwenhuang@126.com.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, 588 Yuhangtang Road, Hangzhou 310058, China; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA; Center for Genetic and Genomic Medicine, James Watson Institute of Genome Sciences, School of Medicine Zhejiang University, 588 Yuhangtang Road, Hangzhou 310058, China. Electronic address: mingqi@zju.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
mesh_terms: D001119:Arginase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D020162:Hyperargininemia / Q000235:genetics*; D007231:Infant, Newborn; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods*
chemical_list: C574619:ARG1 protein, human; D001119:Arginase
keywords: 3D crystal structure; Argininemia; In silico; Newborn screening