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Title: Increasing the genetic diagnosis yield in inherited retinal dystrophies: assigning pathogenicity to novel non-canonical splice site variants
Author: Toulis, Vasileios
Cortés-González, Vianney
Castro-Miró, Marta de
Sallum, Juliana Ferraz
Català-Mora, Jaume
Villanueva-Mendoza, Cristina
Ciccioli, Marcela
Gonzàlez-Duarte, Roser
Valero, Rebeca
Marfany i Nadal, Gemma
Keywords: Malalties de la retina
Retinal diseases
Issue Date: 31-Mar-2020
Publisher: MDPI
Abstract: Aims: We aimed to validate the pathogenicity of genetic variants identified in inherited retinal dystrophy (IRD) patients, which were located in non-canonical splice sites (NCSS). Methods: After next generation sequencing (NGS) analysis (target gene panels or whole exome sequencing (WES)), NCSS variants were prioritized according to in silico predictions. In vivo and in vitro functional tests were used to validate their pathogenicity. Results: Four novel NCSS variants have been identified. They are located in intron 33 and 34 of ABCA4 (c.4774-9G>A and c.4849-8C>G, respectively), intron 2 of POC1B (c.101-3T>G) and intron 3 of RP2 (c.884-14G>A). Functional analysis detected different aberrant splicing events, including intron retention, exon skipping and intronic nucleotide addition, whose molecular effect was either the disruption or the elongation of the open reading frame of the corresponding gene. Conclusions: Our data increase the genetic diagnostic yield of IRD patients and expand the landscape of pathogenic variants, which will have an impact on the genotype-phenotype correlations and allow patients to opt for the emerging gene and cell therapies.
Note: Reproducció del document publicat a:
It is part of: Genes, 2020, vol. 11, num. 4, p. E378
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ISSN: 2073-4425
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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