title: Spectrum of ATP7B mutations and genotype-phenotype correlation in large-scale Chinese patients with Wilson Disease.
abstract: Wilson disease (WD), an inherited disorder associated with ATP7B gene, has a wide spectrum of genotypes and phenotypes. In this study, we developed a rapid multiplex PCR-MassArray method for detecting 110 mutant alleles of interest, and used it to examine genomic DNA from 1222 patients and 110 healthy controls. In patients not found to have any mutation in the 110 selected alleles, PCR-Sanger sequencing was used to examine the ATP7B gene. We identified 88 mutations, including 9 novel mutations. Our analyses revealed p.Arg778Leu, p.Arg919Gly and p.Thr935Met showed some correlations to phenotype. The p.Arg778Leu was related to younger onset age and lower levels of ceruloplasmin (Cp) and serum copper, while p.Arg919Gly and p.Thr935Met both indicated higher Cp levels. Besides, the p.Arg919Gly was related to neurological subtype, and p.Thr935Met showed significant difference in the percentage of combined neurological and visceral subtype. Moreover, for ATP7B mutations, the more severe impact on ATP7B protein was, the younger onset age and lower Cp level presented. The feasibility of presymptomatic DNA diagnosis and predicting clinical manifestation or severity of WD would be facilitated with identified mutations and genotype-phenotype correlation precisely revealed in the study.
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.|Center of Medical Physics and Technology, Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei, China.
authors.forename: N
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.affiliation: Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.affiliation: Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.affiliation: Research Department, Beijing Macro & Micro Test Biotech Co., Ltd, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.affiliation: Research Department, Beijing Macro & Micro Test Biotech Co., Ltd, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002570:Ceruloplasmin / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000073840:Copper-Transporting ATPases / Q000097:blood / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D055815:Young Adult
chemical_list: D002570:Ceruloplasmin; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7B; Wilson disease; correlation; genotype-phenotype; mutations