title: New mutations and polymorphisms of the ATP7B gene in sporadic Wilson disease.
abstract: Wilson's disease (WD) is a rare autosomal recessive genetic disorder of copper metabolism resulting in brain damage, liver failure, and neurological impairment and psychiatric disturbances, as a result of excessive copper accumulation in the brain, liver, kidneys and eyes. ATP7B, encoding a copper transporter P-ATPase was identified as the causative gene of WD. Mutations in the ATP7B gene lead to the defection of the transmembrane transporter so that it can not metabolize copper effectively. We reported the clinical and molecular features of three unrelated and non-consanguineous WD patients. We performed molecular genetic analysis of the ATP7B gene in all cases by DNA sequencing, and revealed 7 novel single nucleotide polymorphisms (SNPs) and 8 well known mutations. Among them, that novel SNP (c. -520 C>T) and two well known mutations (c. 2310 C>G/p. Leu700Leu, c. 2333 G>T/A/p. Arg778Leu/Gln) coexisted in all patients and they were heterozygous and homozygous in the youngest case, respectively, indicating that they may be correlated to the pathogenesis and potentially used as a genetic biomarker for early WD diagnosis.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
authors.forename: Cong-Xia
authors.initials: CX
authors.lastname: Lu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China; Translational Medicine Research Center, School of Pharmaceutical Sciences & Institute for Biomedical Research, Xiamen University, Xiamen, Fujian 361102, China.
authors.lastname: Qing Lin
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences & Institute for Biomedical Research, Xiamen University, Xiamen, Fujian 361102, China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Huang
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences & Institute for Biomedical Research, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: cmtzeng@xmu.edu.cn.
authors.forename: Chi-Meng
authors.initials: CM
authors.lastname: Tzeng
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D001921:Brain / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics*; D002681:China; D000073840:Copper-Transporting ATPases; D003315:Cornea / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7B; Biomarker; Mutation; Single nucleotide polymorphisms (SNPs); Wilson's disease (WD)