Detect The Disease-causing Genes And Clinical Analysis Of A Autosomal Dominant Vitreoretinochoroidopathy Pedigree

Research background and Purpose : ADVIRC is a kind of progressive and irreversible visual impairment disease,posing serious threat to human visual function.The disease has complicated clinical manifestations and high genetic heterogeneity,and the pathogenesis is not yet clear up to now.With the typical characteristics of annular peripheral retinal pigmentation and peripheral retinochoroidal atrophy,the disease is often accompanied by microcornea,microphthalmia,congenital cataract and macular degeneration.Study on the disease-causing gene and mutational spectrumy can not only be beneficial to forecast and provide guidance on having a good birth and good care,improving the early prevention and early diagnostic rate,but understand the pathogenesis on molecular level in order to conduct target gene therapy or tissue therapy on the lesion tissues,cells and genes.With the rapid development of modern molecular biology technology,gene diagnosis technique has continuously improved,nest generation sequencing adopted at present enables simpler,more efficient and more accurate screening of disease-causing gene,promoting the development of genetic diagnosis,even introducing genetic diagnosis to clinical treatment.The article will carry out testing and verification on disease-causing genes and disease-causing mutation through a new method by combining nest generation sequencing technology and eye chip,and analyze of the clinical phenotypic characteristics of the pedigree and its association with mutation genotype in details.Method: We have collected the medical histories of the patients of ADVIRC pedigree and formulated a pedigree chart,ophthalmic testing were conducted to all the family members and made a definitive diagnosis.After they sign informed consent form,draw the peripheral venous blood of family members to store or prepare genomic DNA,Targeted exome sequencing(TES)based on next-generation sequencing(NGS)has been used to discover genetic mutations in large genomic regions for 4 cases,then Sanger sequencing to determine the Candidatedisease-causing genes for the others,and analyze results through bioinformatics technology,and conduct clinical analysisof the pedigree based on clinical phenotype of the disease-causing gene.Result:The clinical manifestations of ADVIRCpedigree: microcornea,congenital cataract,peripheral retinochoroidal atrophy,corneal dystrophy,developing into angle-closure glaucoma in the late stage,BEST-1,c.704TR→C,the heterozygous mutation of the sixth expressed region in which can be found,the mutation sit of the pedigree hasn’t been reported in China.Conclusion: Thephenotype of the ADVIRC pedigree may associated with the c.704TR→Cmutation of BEST1 gene,which is firstly reported in our country.Retina angiography and fundus photography are important testing measures in ADVIRC diagnosis.In some literatures,lack of association of corneal dystrophy with BEST1 gene has been reported,and whether it is caused by BEST1 needs further research.Finally,Targeted exome sequencing(TES)based on next-generation sequencing(NGS)can accurately and efficientlyconduct molecular genetics diagnosis of ADVIRC,improving the detection rate of disease-causing genes and pathogenic mutations.