Identify Pathogenic Variant For Usher Syndrome By Wholeexome Sequencing

ObjectiveIdentify the pathogenic variants of siblings with congenital hearing loss and retinal pigment.MethodsApplication of whole exome sequencing which decipher the code region and 1% size of whole genome,amplified in vitro and parallel sequenced by illumine hiseq 2500.Volume and quality of sequencing was analyzed by bioinformatics methods,coverage and depth were also calculated.GATK was used to detect the SNP and Indel and Annovar was used to annotate the variation.pVAAST was applied to find the candidate pathogenic variant.The allele frequency,Harmfulness and conservation were also analyzed.Sanger sequencing of the whole family was used to test whether the variant were consegrerated.Result1.All individual have 10 G clean data and 80% of them over Q30 quality;2.Average sequencing depth of target region were over 110 X and 99% of these region above 10X;3.MYO7 A was selected the most candidate pathogenic gene by pVAAST;4.the two variant of MYO7 A were not reported by public database,andc.5994G>A was nonsense mutation which will terminate the translation process,anotherc.849+2T>C located near splicing site,scSNV predicted it will damage the splicing process.5.PhastCons analyzed these two variant were in conservation region and Sanger sequencing confirmed the two variant were inherited from their parents repectly.ConclusionWe successfuly find the pathogenic variants for this Usher syndrome family,which will provide basis for clinical genetic diagnosis.