2026-04-13T18:06:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/112802025-10-24T08:28:43Zcom_2072_451660com_2072_378040col_2072_451662

Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma Laguna, Javier Pascual, Beatriz GAMUNDI RODRIGUEZ, MARIA JOSE Borras, Emma Carballo, Miguel MILLA, ELENA Alforja, Socorro HERNAN SENDRA, IMMA [Milla E] Glaucoma, Institut Clínic d'Oftalmologia (ICOF), Hospital Clínic de Barcelona, Barcelona, Spain. Innova Ocular-ICO, Barcelona, Spain. [Laguna J] Servei de Bioquímica i Genètica Molecular, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Barcelona, Spain. [Alforja MS] Glaucoma, Institut Clínic d'Oftalmologia (ICOF), Hospital Clínic de Barcelona, Barcelona, Spain. [Pascual B, Gamundi MJ, Borràs E, Hernán I, Carballo M] Molecular Genetics Unit, Hospital de Terrassa, Terrassa, Spain Consorci Sanitari de Terrassa Glaucoma d'angle obert Glaucoma - Diagnòstic Ulls - Malalties DISEASES::Eye Diseases::Ocular Hypertension::Glaucoma::Glaucoma, Open-Angle Other subheadings::Other subheadings::/diagnosis Other subheadings::Other subheadings::Other subheadings::/genetics ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing ENFERMEDADES::oftalmopatías::hipertensión ocular::glaucoma::glaucoma de ángulo abierto Otros calificadores::Otros calificadores::/diagnóstico Otros calificadores::Otros calificadores::/genética TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::secuenciación de nucleótidos de alto rendimiento Glaucoma primari; Hereditari; Al·lels hipomòrfics Glaucoma primario; Hereditario; Alelos hipomórficos Glaucoma, primary; Hereditary; Hypomorphic alleles Primary open-angle glaucoma (POAG) is a complex disease with a strong hereditably component. Several genetic variants have recently been associated with POAG, partially due to technological improvements such as next-generation sequencing (NGS). The aim of this study was to genetically analyze patients with POAG to determine the contribution of rare variants and hypomorphic alleles associated with glaucoma as a future method of diagnosis and early treatment. Seventy-two genes potentially associated with adult glaucoma were studied in 61 patients with POAG. Additionally, we sequenced the coding sequence of CYP1B1 gene in 13 independent patients to deep analyze the potential association of hypomorphic CYP1B1 alleles in the pathogenesis of POAG. We detected nine rare variants in 16% of POAG patients studied by NGS. Those rare variants are located in CYP1B1, SIX6, CARD10, MFN1, OPTC, OPTN, and WDR36 glaucoma-related genes. Hypomorphic variants in CYP1B1 and SIX6 genes have been identified in 8% of the total POAG patient assessed. Our findings suggest that NGS could be a valuable tool to clarify the impact of genetic component on adult glaucoma. However, in order to demonstrate the contribution of these rare variants and hypomorphic alleles to glaucoma, segregation and functional studies would be necessary. The identification of new variants and hypomorphic alleles in glaucoma patients will help to configure the genetic identity of these patients, in order to make an early and precise molecular diagnosis. 2024-04-03T11:09:14Z 2024-04-03T11:09:14Z 2024-01-19 info:eu-repo/semantics/article Milla E, Laguna J, Alforja MS, Pascual B, Gamundi MJ, Borràs E, et al. Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma. PLoS One. 2024 Jan 19;19(1):e0282133. 1932-6203 https://hdl.handle.net/11351/11280 10.1371/journal.pone.0282133 38241218 http://hdl.handle.net/11351/11280 eng Public Library of Science;19 (1) http://doi.org/10.1371/journal.pone.0282133 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess pdf application/pdf Public Library of Science Scientia