TOP1
Genomic DNA was isolated from peripheral blood samples of the patients using the QIAamp DNA Blood Mini Kit (QIAGEN, 51104). Exome captures were performed with the Agilent SureSelect Human All Exon V6 Kit. Sequencing was then carried out on the Illumina HiSeq X system according to the manufacturers instructions. The average sequencing depth on targets was approximately 107, and the ratio of the target fraction covered at minimum 10 was 99.5%. Sequence reads were aligned to the human genome reference assembly (GRCh37/hg19) by the Burrows Wheeler Aligner (BWA) software. ANNOVAR software was utilized for functional annotation with information from a variety of databases including dbSNP, 1000 Genomes Project, ExAC, Gene Ontology, KEGG and HGMD. The Genome Analysis Toolkit (GATK 3.7) was employed to identify and quality-filter the variants.