title: Identification of three mutations in the MVK gene in six patients associated with disseminated superficial actinic porokeratosis.
abstract: Porokeratosis is recognized as a heterogenously inherited epidermal keratinization disorder. Disseminated superficial actinic porokeratosis (DSAP) is considered to be the most common form of porokeratosis and is characterized by multiple, small keratotic lesions on sun-exposed areas of body. MVK has been reported to be the main candidate gene associated with DSAP. In this study, six sporadic cases of DSAP were clinically characterized. Direct DNA sequencing analysis of the whole coding regions of MVK detected three MVK missense mutations, and two were novel for DSAP: c.31C>T (P11S) and c.1004G>A (G335D). The three mutant MVK proteins were less stable than the wild type protein in different degrees. Mutation G335D also resulted in the misfolding of the ATP binding domain. This study extends the mutation spectrum of MVK. MVK protein stability and correct folding might be the molecular mechanism causing DASP. A 50% probability of detecting a MVK mutation in six DSAP sporadic cases indicated that the MVK gene was useful for clinical characterization, genetic counseling and prenatal diagnosis of DSAP.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
authors.forename: Jiuxiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Archacki
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, Key Discipline of Pharmacy of Hubei Department of Education, Medical College, Hubei Polytechnic University, Huangshi, Hubei 435003, PR China.
authors.forename: Duanzuo
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China. Electronic address: lium@hust.edu.cn.
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D017499:Porokeratosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase
keywords: DSAP; MVK; Mevalonic pathway; Mutation