Clinical Characteristics And Gene Mutation Analysis Of Wilson’s Disease In 24 Patients

Purpose: Wilson’s disease(WD)is an autosomal recessive disorder caused by dysfunction of the ATP7 B gene and defective expression of copper transport proteins,resulting in decreased copper excretion from hepatocytes,leading to hepatocyte toxicity.Excess copper is released into the bloodstream and deposited in several organs including the central nervous system.Most individuals present with liver disease and/or neuropsychiatric symptoms.Regular copper repellent therapy is required as early as possible after diagnosis of WD and requires lifelong medication.Therefore,early diagnosis and treatment are of great importance to improve the prognosis.In this thesis,the clinical data of 24 patients with hepatomegaly were statistically analyzed to assess the phenotypic and genotypic correlation.Methods: Detailed clinical data of 24 patients diagnosed with WD at the Affiliated Hospital of Hangzhou Normal University from January 2015 to October2022 were collected for retrospective analysis,including age,clinical presentation,family history,liver function,coagulation function,copper metabolism index,K-F ring,imaging examination,liver histopathology,and ATP7 B gene mutation loci.Results: 1.There were 24 patients with a male-to-female ratio of 1.4:1,with an age range of 2-65 years and a mean age of onset of 27.29±18.99 years.There were 23 cases of hepatic type and 1 case of mixed type in the clinical typology.2.Liver function indexes ALT,AST,TBi L,ALB,CHE were not statistically significant in patients in the ≥18 years age group versus those in the <18 years age group.The ALP level was significantly higher in patients in the <18 years age group than in the≥18 years age group,which was statistically different and was considered to be related to bone development;coagulation PT and FBG were not statistically different between the two age groups.3.24 patients with WD had a positive CP rate of 100%,a positive 24-hour urine copper rate of 83.3%,a positive K-F rate of 58.3% The detection rates of CP,24-hour urine copper,and K-F ring are high and can be recommended as the first choice of adjuvant examinations;the detection rates of corneal K-F ring and abdominal CT increase with age.4.The liver tissue of WD patients can exhibit any form of liver pathology,such as hepatocellular swelling,ballooning,steatosis,lymphocytic infiltration in the confluent area,and pseudobulbar formation.5.All 24 WD patients were tested for ATP7 B gene,and 15 different ATP7 B allele mutation sites were detected,including 13 missense mutations,one in-frame insertion mutation and one synonymous mutation.The number of p.R778 L mutations accounted for 45.8% and p.P992 L accounted for 29.2%.The most frequent exons were exon 8 and exon 13.6.Two novel mutation sites(p.A1263 P,p.A1074T)and one suspected pathogenic mutation site(p.V1106I)were identified.The protein function prediction of the above three sites was performed using online functional analysis software.The SIFT software predicted that p.A1074 T and p.A1263 P were deleterious variants and p.V1106 I was benign;the Polyphen2 software predicted that all three variants were deleterious variants.7.Genetic testing is a valuable tool for diagnosing WD,and it is important for early genetic diagnosis and genetic counseling for WD pre-documented individuals and their family lines,but genetic results cannot exclude WD.8.The results showed no statistically significant differences in ALT,AST,CP,24 h urine copper levels,number of cirrhotic abdominal CT cases,and number of positive K-F rings between the three groups.9 WD is one of the few genetic diseases that can be effectively controlled.Early detection,diagnosis and regular copper repellent treatment at the earliest possible stage are essential to improve prognosis and delay or avoid the development of serious complications.Conclusion: WD can develop at all ages,and the clinical phenotype in this study is predominantly hepatic;CP,24-hour urine copper,and the K-F loop have a high positive detection rate in WD patients and can be recommended as the first choice of ancillary tests;p.R778 L and p.P992 L are the two most common mutant loci in this study;a total of two new mutant loci(p.A1263 P,p.A1074T)and one suspected pathogenic mutant loci(p.V1106I)were identified.This study examined the genotype and phenotype of some patients and did not find any correlation between them;early detection,diagnosis and treatment are essential for WD to improve prognosis and delay or avoid the occurrence of serious complications.