The Research Of The Cystogenesis Of Autosomal Dominant Polycystic Kidney Disease

Background:Autosomal dominant polycystic kidney disease?ADPKD?is a common Mendelian disease,mutated by PKD1 or PKD2 gene and affects lin 400 to 1 in 1000 live births worldwide.About half of people with ADPKD have end stage renal disease?ESRD?by age 60years.ADPKD is generally a late-onset multisystem disorder characterized by the development and progressive enlargement of cysts in the kidneys and extrarenal organs including the liver,seminal vesicles,arachnoid membrane,and pancreas.It's a very serious diesaese in hunman body.Now there have no effective drugs to cure ADPKD.Objective:To identify the responsible mutation of autosomal dominant polycystic kidney disease?ADPKD?in two family,Screening the mutations of polycystic kidney disease gene 1?PKD1?and polycystic kidney disease gene 2?PKD2?towards precision medicine.Such studies provide a natural bridge from genetic changes to phenotypes,thus can help elucidate the mechanism of how variants affect disease.Methods:Five Chinese families?the Han nationality?were diagnosed with ADPKD according to standard criteria and recuited in the research.Genomic DNA was extractrd from all aviliable blood sample and one tissue sample.In the present study,the mutation analysis of PKD genes was performed in five Chinese families with ADPKD using PCR and targeted next generation sequencing.Using STR for linkage and testing LOH are to find somatic mutations.This study was approved by Ethic Committee of the First People's Hospital of Yunnan Province,Affiliated Hospital of Kunming University of Science and Technology.Results:?1?Three new mutation?PKD2c.1094 +1₊4delGTAA;PKD2 c.1393T>C;PKD1 c.10885delA?of the PKD gene was identified in five families targeted next-generation sequencing.what's more.Two suspected mutation?PKD1:c.6832G>T,PKD1 c.6778₆780delATT?of the PKD1 gene was identified in a two affected family members,but not in unaffected relatives or unrelated controls.so they are confirmed pathogenic mutation.?2?there have LOH found in Family 1 proband tissue.Conclusion:?1?The variants of mutations are much different from European and North America countries,its may be correlated with itself natural environment.?2?Somatic mutation of the PKD gene doesn't play important role in the cystogenesis of Autosomal dominant Polycystic kidney disease.