2026-06-14T03:33:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/172632025-06-26T10:59:56Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609col_20.500.12105_19616

00925njm 22002777a 4500 dc Rodriguez-Martin, Carlos author Cidre, Florencia author Fernández-Teijeiro, Ana author Gomez-Mariano, Gema Maria author de la Vega, Leticia author Ramos, Patricia author Zaballos, Ángel author Monzon-Fernandez, Sara author Alonso, Javier author 2016-05 Retinoblastoma (RB, MIM 180200) is the paradigm of hereditary cancer. Individuals harboring a constitutional mutation in one allele of the RB1 gene have a high predisposition to develop RB. Here, we present the first case of familial RB caused by a de novo insertion of a full-length long interspersed element-1 (LINE-1) into intron 14 of the RB1 gene that caused a highly heterogeneous splicing pattern of RB1 mRNA. LINE-1 insertion was inferred by mRNA studies and full-length sequenced by massive parallel sequencing. Some of the aberrant mRNAs were produced by noncanonical acceptor splice sites, a new finding that up to date has not been described to occur upon LINE-1 retrotransposition. Our results clearly show that RNA-based strategies have the potential to detect disease-causing transposon insertions. It also confirms that the incorporation of new genetic approaches, such as massive parallel sequencing, contributes to characterize at the sequence level these unique and exceptional genetic alterations. J Hum Genet. 2016 May;61(5):463-6. 10.1038/jhg.2015.173 1435-232X Journal of human genetics 26763876 http://hdl.handle.net/20.500.12105/17263 Familial retinoblastoma due to intronic LINE-1 insertion causes aberrant and noncanonical mRNA splicing of the RB1 gene