Mapping The Pathogenic Gene For A Pedigree With Primary Angle-Closure Glaucoma

Objective:To collect and analyse the clinical phenotypes of a pedigree with primary angle-closure glaucoma,and to determine the genetic characteristics by whole-exome sequencing,so as to identify the potential causative genes.Methods:1.Collected data of family members through field visits and field surveys,detailed the medical history,analyzed and determined the phenotype and mode of inheritance;2.Selected 3 diseased members(cases group)and 2 normal members(controls group)from this pedigree,obtained their peripheral blood,extracted blood DNA,and assessed the quality of DNA.3.Captured and enriched exons areas by using capture chips,sequenced all exons after the preparation of qualified library,filtered the raw data to obtain the valid data,then carried on the precision of bioinformatics analysis,detailed annotations and advanced analysis,finally got the potential causative genes,and verified these candidate gene mutations.Results:1.A pedigree with primary angle-closure glaucoma was collected,which had more than 20 members from 5 generations(including 6 patients,2 males and 4 females);And 15 members existed from 3 generations when sampled in May,2018(including 3 patients,1male and 2 female).2.DNA samples from 5 family members were extracted for quality testing,and their quality,concentration and purity met the requirements;3.Completed whole exome sequencing in all of these DNA samples,found five potential specific causative genes,including KIF5B/PCK2 / UNC13C/DSG1 / PSEN2 respectively,and these genes were verifid eventually.Conclusions:1.A typical PACG family was collected with clear genetic relationship,large number of patients and prominent phenotypic characteristics,which conformed to the autosomal dominant genetic mode,providing a good basic condition for our study and enriching the genetic resource information of glaucoma;2.The quality,concentration and purity of the extracted DNA samples all met the quality inspection requirements,which not also increased the feasibility of the sequencing and the credibility of the results,but also laid a reliable foundation for the research on molecular genetics;3.Completed whole exome sequencing for this family,and 5 potential specific pathogenic genes were finally identified,providing a basis for further elucidation of pathogenic genes of primary angle-closure glaucoma and playing an important role in gene screening,gene diagnosis and gene therapy of this disease in the future.