講演情報
[O24-3]全ゲノム解析を契機に同定したモザイク欠失の検証
○土田 奈緒美1,2, 内山 由理1,2, 濱中 耕平1, 岡本 伸彦3, 藤本 礼尚4, 榎 日出夫4, 輿水 江里子1, 藤田 京志1, 三澤 計治1, 宮武 聡子1,5, 水口 剛1, 松本 直通1 (1.横浜市立大学 大学院医学研究科 遺伝学, 2.横浜市立大学附属病院 難病ゲノム診断科, 3.大阪母子医療センター 遺伝診療科, 4.聖隷浜松病院 てんかんセンター, 5.横浜市立大学附属病院 遺伝子診療科)
Structural variants (SVs) involving genes as well as single nucleotide variants (SNVs) and indels are important in the etiology of rare genetic diseases. Whole genome sequencing (WGS) is a powerful technology detecting SVs. In this study, we applied short-read WGS analyses to two patients with neurodevelopmental disorders (one with Coffin-Siris syndrome, and the other with epilepsy and mild developmental delay), both of whom were undiagnosed by trio-based whole exome sequencing (WES), and WGS could successfully identified likely pathogenic deletions in both cases. Both deletions could be missed by copy-number variation (CNV) analysis using WES data; one was a 1469 bp deletion involving only a single exon of ARID1B, and the other was a 148 kb deletion involving 5' untranslated region in MBD5 which is outside of WES-targeted regions. These deletions were confirmed with multiple methods, including IGV inspection of WGS data, breakpoint PCR, quantitative PCR, and digital PCR. In both deletions, the mosaicism could be involved and its contribution to the pathogenesis will be discussed.