The Study Of Clinical Features And Analysis Of Chromosome And Whole Exome Sequencing Of Twins With Biliary Atresia

Objective:The goals of this study were to investigate the prevalence,clinical features and prognosis of twins with biliary atresia(BA)and pregnancy status of twin's mother,from 2012 to 2016 in 7 medical centers in mainland China.By detecting the chromosome G-banding karyotype and whole exome sequencing of three sets of monozygotic twins with biliary atresia,to preliminary study the genetic backgrounds of biliary atresia.Methods:1.To retrospective analyse the clinical information,treatments,prognosis and follow-up data of twins with biliary atresia and pregnancy status of mothers during pregnance,from March 2012 to June 2016 in 7 medical institutions in mainland China.2.Collecting the peripheral venous blood samples from three pairs of monozygotic twins with biliary atresia,to detect the chromosome G-banding karyotypes and whole exome sequencing respectively and to analyse the genetic backgrounds of biliary atresia.Results:1.Demographic Data A total of about 1,200 biliary atresia cases occurred during the period in 7 medical centers in mainland China,15 sets of twins with biliary atresia were included in our study,6 pairs of monozygotic twins,9 pairs of dizygotic twins.In our study,there was only one infant affected BA in each pair of twins,the other co-twin was born healthy;2.Treatments Kasai operation: 13 cases of twins with biliary atresia underwent kasai procedure,and the rest 2 cases underwent exploratory laparotomy surgery(ELS);liver transplantation: 7 cases of children eventually underwent liver transplantation,including 6 BA patients who had undergone kasai operation and 1 patient who had received ELS;3.Prognosis Eight cases of patients presented jaundice-free and the rest 5 cases showed persistent jaundice after kasai operation;8 cases occured cholangitis during the 3-53 months follow-up period,6 patients survive well with their native liver after kasai surgery;7 cases received liver transplantation ultimately and achieved a good postoperative course;1 case who had received kasai operation was loss to follow-up at the 2 years old;1 case who had undergone ELS died at 2 years of age.4.Pregnant status All mothers who delivered twins had good health condition and did not have underlying diseases.The results of prenatal screening tests were normal.Two pregnant women suffered from gestational hypertension,one occurred gestational diabetes mellitus,and the others were healthy during pregnancy;None of women was detected viral infection during pregnancy.Father was in good condition,there was no family history of similar diseases.5.The results of Chromosome G with karyotype analysis of three monozygotic twins with biliary atresia were normal,46,XX/46 XY.6.The whole exome sequencing results showed that no differential genotypes,SNPs,Indels and CNVs were detected between monozygotic twins with biliary atresia.Conclusion:The occurance of biliary atresia was lower.In this study,twins with biliary atresia is only 1.25% of the general populations of BA.There was only one infant had biliary atresia in each set of twin.The rate of jaundice-free within 6 months after surgery was 61.5%,rate of cholangitis was 61.5% and the overall survival rate was 86.7%,of these patients achieved a good postoperative courses.Results of chromosome karyotype and the whole-exome sequencing showed normal and no differential genotypes between the monozygotic BA twins with discordant clinical phenotypes,which suggests that this disease may not be a simple hereditary disease,the genetic phenotype or genepenetrance and other factors may contribute to the occurrence of BA.