Mutational Characterization Of ATP7B In Southeastern Chinese Patients With Wilson's Disease And Analysis Of The Special Phenotype

Wilson's disease is an autosomal recessive copper metabolism disorder,characterized by the progressive extrapyramidal symptoms and hepatic damage.The p disease-causing gene is ATP7B,which encodes a P-type ATPase and involves in the liver's copper metabolism.At present,more than 500 pathogenic mutations and about 100 non-pathogenic variants of ATP7B have been reported,distributed throughout the entire length of the gene.Therefore,the genotype of patients with Wilson's disease is very complex,and the mutation pattern varies among different populations and areas.In this study,118 unrelated families and 123 patients of Wilson's disease with genetic testing from Eastern China were enrolled in this study.There were 59 patients(48.0%)with onset of neurological symptoms,15 patients(12.2%)with onset of symptoms of liver disease,6 patients(4.9%)with onset of skeletal symptoms,4 patients(3.3%)with psychiatric symptoms and 39 asymptomatic patients(31.7%).We identified 64 mutations in the 128 proband,and the most frequent mutations were p.R778L(34.15%),p.P992L(15.45%)and p.A874V(3.66%).We compared the differences in clinical parameters between different clinical groups and different genotypes,including age of onset,age of neurological symptoms,serum ceruloplasmin,24 h urinary copper,routine blood count,liver and kidney function,routine lipid,bone metabolic parameters and electrolyte.We found that patients with p.R778L homozygous mutations had lower serum ceruloplasmin levels and those with p.V1106I mutations had elder age of onset of neurological symptoms and higher serum ceruloplasmin levels,which highly suggested an association with late-onset Wilson's disease.In addition,we reported the 13 patients with bone and joint symptoms as the first symptoms during the past ten years,aiming to improve early diagnosis and therapy with this condition.