Genomics · 2022
Pathogenic variants detected by RNA sequencing in Cornelia de Lange syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Seyama Rie, Uchiyama Yuri, Ceroni José Ricard Magliocco, Kim Veronica Eun Hue, Furquim Isabel, Honjo Rachel Sayuri, Castro Matheus Augusto Araujo, Pires Lucas Vieira Lacerda, Aoi Hiromi, Iwama Kazuhiro, Hamanaka Kohei, Fujita Atsushi, Tsuchida Naomi, Koshimizu Eriko, Misawa Kazuharu, Miyatake Satoko, Mizuguchi Takeshi, Makino Shintaro, Itakura Atsuo, Bertola Débora R, Kim Chong Ae, Matsumoto Naomichi
Аннотация
Recent studies suggest that transcript isoforms significantly overlap (approximately 60%) between brain tissue and Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs). Interestingly, 14 cohesion-related genes with variants that cause Cornelia de Lange Syndrome (CdLS) are highly expressed in the brain and LCLs. In this context, we first performed RNA sequencing of LCLs from 22 solved (with pathogenic variants) and 19 unsolved (with no confirmed variants) CdLS cases. Next, an RNA sequencing pipeline was developed using solved cases with two different methods: short variant analysis (for single-nucleotide and indel variants) and aberrant splicing detection analysis. Then, 19 unsolved cases were subsequently applied to our pipeline, and four pathogenic variants in NIPBL (one inframe deletion and three intronic variants) were newly identified. Two of three intronic variants were located at Alu elements in deep-intronic regions, creating cryptic exons. RNA sequencing with LCLs was useful for identifying hidden variants in exome-negative cases.