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oai:repisalud.isciii.es:20.500.12105/114202025-06-25T10:29:40Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16939col_20.500.12105_19616col_20.500.12105_25179

00925njm 22002777a 4500 dc Rodriguez-Martin, Carlos author Robledo, Cristina author Gomez-Mariano, Gema Maria author Monzon-Fernandez, Sara author Sastre, Ana author Abelairas, Jose author Sabado, Constantino author Martín-Begué, Nieves author Ferreres, Joan Carles author Fernández-Teijeiro, Ana author González-Campora, Ricardo author Rios-Moreno, María José author Zaballos, Ángel author Cuesta de la Plaza, Isabel author Martinez-Delgado, Beatriz author Posada De la Paz, Manuel author Alonso, Javier author 2020-01 Somatic mutational mosaicism is a common feature of monogenic genetic disorders, particularly in diseases such as retinoblastoma, with high rates of de novo mutations. The detection and quantification of mosaicism is particularly relevant in these diseases, since it has important implications for genetic counseling, patient management, and probably also on disease onset and progression. In order to assess the rate of somatic mosaicism (high- and low-level mosaicism) in sporadic retinoblastoma patients, we analyzed a cohort of 153 patients with sporadic retinoblastoma using ultra deep next-generation sequencing. High-level mosaicism was detected in 14 out of 100 (14%) bilateral patients and in 11 out of 29 (38%) unilateral patients in whom conventional Sanger sequencing identified a pathogenic mutation in blood DNA. In addition, low-level mosaicism was detected in 3 out of 16 (19%) unilateral patients in whom conventional screening was negative in blood DNA. Our results also reveal that mosaicism was associated to delayed retinoblastoma onset particularly in unilateral patients. Finally we compared the level of mosaicism in different tissues to identify the best DNA source to identify mosaicism in retinoblastoma patients. In light of these results we recommended analyzing the mosaic status in all retinoblastoma patients using accurate techniques such as next-generation sequencing, even in those cases in which conventional Sanger sequencing identified a pathogenic mutation in blood DNA. Our results suggest that a significant proportion of those cases are truly mosaics that could have been overlooked. This information should be taking into consideration in the management and genetic counseling of retinoblastoma patients and families. J Hum Genet. 2020 Jan;65(2):165-174. 10.1038/s10038-019-0696-z 1435-232X 1434-5161 Journal of human genetics 31772335 http://hdl.handle.net/20.500.12105/11420 Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.