One Cases Of Rare Imaging Changes And The Study On Pathogenicity Of New Missense Mutations Of Wilson's Disease

Purpose:To improve the early diagnosis of Hepatolenticular Degeneration(HLD)through analysis of rare HLD imaging and the suspected new missense mutations of gene(ATP7B)in a HLD patient.Method:1.To collect and analyze clinical data of a HLD patient with rare MRI imaging and detect the mutations of the ATP7 B gene.2.To review the rare imaging changes in HLD by selecting reported HD cases between the time 1997 to April of 2018 with imaging changes in white matter through searching the CNKI,Wanfang,Pubmed and other databases with these key words:“???????????Hepatolenticular degeneration?MRI”.3.Mutations were detected by Sanger sequencing in Four Exons(8,12,13,16)in ATP7 B gene of this patient.According to the standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics(ACMG)and Genomics and the Association for Molecular Pathology(AMP),we used the biological information analysis software Polyphen2 and SIFT to estimate the pathogenicity of new missense mutations of ATP7 B gene in this patient.Results:1.20 HD patients(14 male and 6 female)with rare MRI imaging were collected,aged 9~46 years old,with an average age of 19.45±8.67 years.The case data summary is as follows:(1)19 cases had abnormal MRI signals in frontal lobe,4 cases in temporal lobe,9 cases in parietal lobe;(2)10 patients experienced epilepsy(50%);(3)All these patients had extrapyramidal symptoms;(4)3 patients showed psychiatric symptoms(15%),mental decline was found in 8 patients(40%);(5)11 patients had abnormal function of liver and spleen(78.57%);(6)2 patients with epilepsy had gyrus enhancement in MRI with contrast;(7)Rare MRI imaging appeared in 9 patients after the treatment of decoppering(45%);(8)6 patients experienced epileptic seizures following decoppering treatment;(9)Abnormal MRI signals in frontal lobe in 1 patient decreased after 4 years of decoppering and antiepileptic treatment,and abnormal MRI signals in white matter appeared in 1 patient after the treatment of penicillamine?2.We used the biological information analysis software Polyphen2 and SIFT to estimate the pathogenicity of mutation site c.2731G>A;p.A911 T in ATP7 B gene of this patient which was detected by Sanger sequencing.The prediction results of Polyphen2 scored 1(0~1),while the sensitivity scored 0 and the specificity scored 1.The SIFT prediction results scored <0.05,suggesting that the substitution of 911 st bits from A to T is expected to affect the function of Copper-transporting ATPase2 expressed by the ATP7 B gene.Combined the gene testing result of the parents,the mutation site of c.2333G>T;p.R778 L was inherited from the patient's mother,and c.2731G>A;p.T911 A was inherited from the patient's father.Conclusion:1.Knowledge of rare symptoms and imaging features of HLD is helpful for the early diagnosis of HLD.2.Mutation detection of ATP7 B gene is a reliable measure for HLD diagnose and identify the pathogenicity mutation sites.