Analysis Of Polycystic Liver Disease With Polycystic Kidney Disease In Chinese Han Adults And Identification Of Mutated Genes

Objects:The whole exome sequencing was performed on a patient with polycystic liver and polycystic kidney disease and its family members,so as to make accurate gene diagnosis for the proband,to explore the genetic mode of the disease in the family,to carry out population analysis on the mutation site,to expand the Chinese PLD pathogenic gene spectrum,and to provide theoretical basis for genetic counseling and gene diagnosis.Methods:1.A patient with a clear family history of polycystic liver with polycystic kidney disease was collected.Then we investigated the family information and collected the clinical data and peripheral blood samples of 14 immediate relatives in the family to draw the family map.2.Confirmed the kinship of 14 subjects in this family.Then we selected four core samples,namely the proband(Ⅱ-2),the lover of the proband(Ⅱ-1),the sick son of the proband(Ⅲ-2)and the healthy daughter of the proband(Ⅲ-5)for whole exome sequencing.First,the common mutations of the proband and the sick son were screened out,and then the mutations in the proband’s lover and the healthy daughter of the proband were excluded.Finally,the mutation sites were screened by database comparison.3.The mutation prediction software was used to analyze the effect of mutation site on protein function.4.The mutation site was verified by Sanger in 14 subjects.Results:1.According to the analysis of pedigree map and WES results,the disease conforms to the autosomal dominant inheritance pattern in the family line,and the clinical manifestations of the disease are highly heterogeneous.2.WES and database comparison revealed the suspected GANAB c.1118c>T(p.T373I)mutation in the pedigree.3.Analysis of various mutation prediction software indicated that this mutation caused serious damage to the protein encoded by GANAB gene and was a pathogenic mutation.4.Sanger results showed that all diseased members of the family carried GANAB c.1118C>T(p.T373I)mutation,and none of the healthy members carried this mutation site.In addition,this mutation site is the first in the world and is a newly discovered pathogenic mutation site.Conclusion:1.This study found a rare case of polycystic liver with polycystic kidney.2.The pathogenic mutation in this pedigree is the newly discovered heterozygous mutation on GANAB c.1118C>T(p.T373I),which has not been reported at home and abroad and is a newly discovered PLD pathogenic mutation site.