1. Research On The Genetic Characteristics Of Caroli Disease Family—using Whole-exome Sequence Sequencing To Detect PKHD1 Gene Mutation 2. Neuroblastoma And Hepatoblastoma RECK And Related MMPs Expression And Comparative Analysis Of Tumor Metastasis

Part 1Whole Exome Sequencing Identifies Recessive PKHD1 Mutations in a Chinese Twin Family with Caroli DiseaseObjective Mutations in PKHD1 cause autosomal recessive Caroli disease,which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts.However,the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established.Methods Whole exome sequencing(WES)was performed on one twin sample with Caroli disease from a Chinese family from Shandong province.Routine Sanger sequencing was used to validate the WES and to carry out segregation studies.We also described the PKHD1 mutation associated with the genotype-phenotype of this twin.Results A combination of WES and Sanger sequencing.revealed the genetic defect to be a novel compound heterozygous genotype in PKHD1,including the missense mutation c.2507 T>C,predicted to cause a valine to alanine substitution at codon 836(c.2507T>C,p.Val836A1a),and the nonsense mutation c.2341C>T,which is predicted to result in an arginine to stop codon at codon 781(c.2341C>T,p.Arg781*).This compound heterozygous genotype co-segregates with the Caroli disease-affected pedigree members,but is absent in 200 normal chromosomes.Conclusions Our findings indicate exome sequencing can be useful in the diagnosis of Caroli disease patients and associate a compound heterozygous genotype in PKHD1 with Caroli disease,which further increases our understanding of the mutation spectrum of PKHD1 in association with Caroli disease.Part 2The Expression of RECK and MMPs in NB and HB and Researches on Comparative Analysis in their MetastasisObjective To detect the expression of RECK(reversion-inducing cysteine-rich protein with Kazal motifs),MMPs(matrix metalloproteinase)in neuroblastoma and hepatoblastoma to investigate the different expression of transfer characteristics in both tumor.Methods We used PV-6000 immunohistochemistry to measure the expression of RECK and MMPs in neuroblastoma and hepatoblastoma.Results The expression rate of RECK in the hepatoblastoma tissues is higher than neuroblastoma,MMPs has obvious significance in the both tumor transfer characteristics,Neuroblastoma has a stronger infiltration characteristics than hepatoblastoma.The expression of RECK was negatively correlated with the expression of MMPs.Conclusions The expression of RECK in hepatoblastoma tissues is higher than neuroblastoma,The expression of RECK and MMPs is negatively correlated associated with tumor metastasis and invasion.