Deciphering the etiology of undiagnosed ocular anomalies along with systemic alterations in pediatric patients through whole exome sequencing.

Autor: Reyna-Fabián ME; Laboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Mexico City, Mexico., Fernández-Hernández L; Laboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Mexico City, Mexico., Enríquez-Flores S; Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Mexico City, México., Apam-Garduño D; Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, México.; Departamento de Genética, Asociación Para Evitar la Ceguera en México, Vicente García Torres No. 46 Barrio San Lucas, Coyoacán, C.P. 04030, Mexico City, México., Prado-Larrea C; Departamento de Glaucoma, Asociación Para Evitar la Ceguera en México, Mexico City, México., Seo GH; Medical Genetics Division, 3Billion, Inc., Seoul, South Korea., Khang R; Medical Genetics Division, 3Billion, Inc., Seoul, South Korea., Cortés-González V; Departamento de Genética, Asociación Para Evitar la Ceguera en México, Vicente García Torres No. 46 Barrio San Lucas, Coyoacán, C.P. 04030, Mexico City, México. vianney.cortes@apec.com.mx.; Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico. vianney.cortes@apec.com.mx.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jun 22; Vol. 14 (1), pp. 14380. Date of Electronic Publication: 2024 Jun 22.
DOI: 10.1038/s41598-024-65227-6
Abstrakt: Inherited and developmental eye diseases are quite diverse and numerous, and determining their genetic cause is challenging due to their high allelic and locus heterogeneity. New molecular approaches, such as whole exome sequencing (WES), have proven to be powerful molecular tools for addressing these cases. The present study used WES to identify the genetic etiology in ten unrelated Mexican pediatric patients with complex ocular anomalies and other systemic alterations of unknown etiology. The WES approach allowed us to identify five clinically relevant variants in the GZF1, NFIX, TRRAP, FGFR2 and PAX2 genes associated with Larsen, Malan, developmental delay with or without dysmorphic facies and autism, LADD1 and papillorenal syndromes. Mutations located in GZF1 and NFIX were classified as pathogenic, those in TRRAP and FGFR2 were classified as likely pathogenic variants, and those in PAX2 were classified as variants of unknown significance. Protein modeling of the two missense FGFR2 p.(Arg210Gln) and PAX2 p.(Met3Thr) variants showed that these changes could induce potential structural alterations in important functional regions of the proteins. Notably, four out of the five variants were not previously reported, except for the TRRAP gene. Consequently, WES enabled the identification of the genetic cause in 40% of the cases reported. All the syndromes reported herein are very rare, with phenotypes that may overlap with other genetic entities.
(© 2024. The Author(s).)
Databáze: MEDLINE
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