Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene

[Background] Biallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which struct...

Descripción completa

Detalles Bibliográficos
Autores: Fernández-Suárez, Elena, González del Pozo, María, Méndez-Vidal, Cristina, Martín-Sánchez, Marta, Mena, Marcela, Morena-Barrio, Belén de la, Corral, Javier, Borrego, Salud, Antiñolo, Guillermo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/388170
Acceso en línea:http://hdl.handle.net/10261/388170
https://api.elsevier.com/content/abstract/scopus_id/85192051925
Access Level:acceso abierto
Palabra clave:Retrotransposon
EYS
Alu insertion
CNV
Inherited retinal diseases
Long-read sequencing
Nanopore sequencing
Retinitis pigmentosa
Descripción
Sumario:[Background] Biallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which structural variants (SVs) represent a common cause of disease. However, their identification using short-read sequencing (SRS) is not always feasible. Here, we conducted targeted long-read sequencing (T-LRS) using adaptive sampling of EYS on the MinION sequencing platform (Oxford Nanopore Technologies) to definitively diagnose an arRP family, whose affected individuals (n = 3) carried the heterozygous pathogenic deletion of exons 32–33 in the EYS gene. As this was a recurrent variant identified in three additional families in our cohort, we also aimed to characterize the known deletion at the nucleotide level to assess a possible founder effect.