Low grade mosaicism in hereditary haemorrhagic telangiectasia identified by bidirectional whole genome sequencing reads through the 100,000 Genomes Project clinical diagnostic pipeline

作者：Jessica M Clarke, Mary Alikian, Sihao Xiao, Dalia Kasperavičiūtė, Ellen Thomas, Isobel G. Turbin, Kike Olupona, Elna Cifra, Emanuel Curetean, Teena Ferguson, Julian Redhead, Claire L. Shovlin · 发表于：Journal of Medical Genetics · 年份：2020 · DOI：10.1136/jmedgenet-2019-106794 · 被引用次数：19 · 研究领域：Vascular Anomalies and Treatments、Tracheal and airway disorders

For rare inherited diseases an important question is what type of clinical diagnostic test to select, for instance Sanger-based single genesequencing; a high read depth gene panel; whole exomesequencingor whole genome sequencing. There is emerging recognitionthat a transmissible parental variant present at less than expected heterozygous frequency (due to mosaicism) may escape detection by certain methods. This risk has been proposed as a factor infavourof higher depth sequencingstrategies. Here we report a case where barely 30-fold depth whole genome sequencing through the 100,000 Genomes Project identified low grade mosaicismthat had been missed by conventional Sanger sequencing.