A Study On ATP7B Gene Mutation In A Wilson's Disease Family

Objective A case of hepatolenticular degeneration and its parent's ATP7 B genes were detected.Meanwhile,the retrospective analysis of the pathogenicity of hepatolenticular degeneration in recent years was carried out to study the relationship between genotype and phenotype.So as to pay more attention to the disease in clinic,reduce misdiagnosis diagnosis and treatment.Making a contribution to the new pathogen for the diagnosis and treatment of Wilson's disease.Methods ATP7 B mutations were detected by molecular biology techniques such as human genomic DNA extraction,polymerase chain reaction(PCR)and DNA sequencing.After the second generation of sequencing results,the accuracy of the former results was verified by Sanger generation sequencing.The data of ATP7 B gene and its sex,age,clinical type,serum ceruloplasmin and urinary copper were analyzed.The genotype and clinical characteristics of ATP7 B gene were analyzed by biology and blood routine.Phenotype.Secondly,by retrospectively analyzing patients with hepatolenticular degeneration,the hot spots of ATP7 B genotype and the distribution of high frequency mutations were analyzed.According to the clinical data such as age,sex,type of disease and the severity of illness,we analyzed the relationship between the genotype and phenotype of the disease to obtain definitive results.Results The pediatric ATP7B-exon11 gene has missense mutations(c.2621C> T),2621 bases from C(cytosine)to T(thymine),the 874 codons from GCG to GTG,it's the encoded product changed from arginine(Arg)to valine(Val);the mother's ATP7B-exon8 gene was misaligned(c.2333G> T),and the 2333 base was changed from G(guanine)For T(thymine),the 778 codons from CGG to CTG,the encoded product from arginine(Arg)to leucine(Leu).Two mutant gene carriers inherit the causative gene to the offspring,causing the proband to be sick.Generation of sequencing results yielded the same result.Laboratory findings showed that the proband had abnormal liver function.Through a retrospective analysis ofthe relevant literature for the past five years,we received a total of 255 patients.Found that the mutation of the Chinese hot spots for the R778 L,mutation rate of 38.04%.The main mutation type was missense mutation,mutation rate was 92.97%.There was no significant difference between different genotypes and phenotypes.Conclusion Patients with hepatolenticular degeneration have inherited the recessive genes of parents who are carriers of pathogenic genes,and even if the genotypes of the mutant genes are diverse,their pathogenesis and clinical manifestations are not significantly different.The proband appears abnormal liver function,showing that the disease first accumulates the liver.The parents of the relevant laboratory tests are more normal,showing that simply carry the pathogen gene does not cause the expression of the relevant protein abnormalities.Imaging examination shows the normal size of the organ of the proband,can be seen if the early onset of timely diagnosis and treatment,will effectively intervene in the course of progress,and after follow-up treatment is very good prognosis.Of the 255 patients reviewed,251 were detected mutations,and four were still unable to detect mutations,possibly because the mutations in the four patients were not located on the exon and may be present in the intron or an exon to intron link.It is best to be able to obtain genetic analysis of the complete family of probands,but it is very difficult to accomplish in practice.Therefore,for the probate parents of their compatriots,they may also be carriers of pathogenic genes.Therefore,for potential carriers,genetic testing is necessary.Especially for those who are about to give birth to the next generation,to check whether they are carriers of pathogenic genes,is even more important.At the same time for parents who have been born sick children,before the second child's delivery,a gene screening for the fetus and genetic counseling are very necessary.