Pathogenic variants detected by RNA sequencing in Cornelia de Lange syndrome

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Citações na Scopus
1
Tipo de produção
article
Data de publicação
2022
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS INC ELSEVIER SCIENCE
Autores
SEYAMA, Rie
UCHIYAMA, Yuri
CERONI, Jose Ricard Magliocco
AOI, Hiromi
IWAMA, Kazuhiro
Citação
GENOMICS, v.114, n.5, article ID 110468, 13p, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Aberrant splicing, Cornelia de Lange syndrome, Genetic analysis, RNA sequencing, Whole exome sequencing
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