Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/195344
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Genes and variants underlying human congenital lactic acidosis—from genetics to personalized treatment |
Autor: | Bravo-Alonso, Irene; Navarrete, Rosa; Vega, Ana Isabel; Ruíz-Sala, Pedro; García Silva, María Teresa; Martín-Hernández, Elena; Quijada-Fraile, Pilar; Belanger-Quintana, Amaya; Stanescu, Sinziana; Bueno, María; Vitoria, Isidro; Toledo, Laura; Couce, María Luz; García-Jiménez, Inmaculada; Ramos-Ruiz, Ricardo CSIC ORCID; Martín, Miguel Ángel; Desviat, Lourdes R. CSIC ORCID; Ugarte, Magdalena CSIC ; Pérez-Cerdá, Celia; Merinero, Begoña CSIC; Pérez, Belén CSIC ORCID; Rodríguez-Pombo, Pilar CSIC ORCID | Palabras clave: | Congenital lactic acidosis Mitochondrial dysfunction Metabolomics datasets Clinical-exome sequencing RNA analysis Antisense therapy for mitochondrial disorders Healthcare Mitochondrial morphology |
Fecha de publicación: | 1-nov-2019 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | Journal of Clinical Medicine 8(11): 1811 (2019) | Resumen: | Congenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn errors of metabolism that result in defective mitochondrial function. Even though the implementation of next generation sequencing has been rapid, the diagnosis rate for this highly heterogeneous allelic condition remains low. The present work reports our group’s experience of using a clinical/biochemical analysis system in conjunction with genetic findings that facilitates the taking of timely clinical decisions with minimum need for invasive procedures. The system’s workflow combines different metabolomics datasets and phenotypic information with the results of clinical exome sequencing and/or RNA analysis. The system’s use detected genetic variants in 64% of a cohort of 39 CLA-patients; these variants, 14 of which were novel, were found in 19 different nuclear and two mitochondrial genes. For patients with variants of unknown significance, the genetic analysis was combined with functional genetic and/or bioenergetics analyses in an attempt to detect pathogenicity. Our results warranted subsequent testing of antisense therapy to rescue the abnormal splicing in cultures of fibroblasts from a patient with a defective <i>GFM1</i> gene. The discussed system facilitates the diagnosis of CLA by avoiding the need to use invasive techniques and increase our knowledge of the causes of this condition. | Versión del editor: | https://doi.org/10.3390/jcm8111811 | URI: | http://hdl.handle.net/10261/195344 | DOI: | 10.3390/jcm8111811 | E-ISSN: | 2077-0383 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
genes_lactic_acidosis_personalized_treatment.pdf | 2,08 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
8
checked on 03-may-2024
SCOPUSTM
Citations
10
checked on 03-may-2024
WEB OF SCIENCETM
Citations
10
checked on 29-feb-2024
Page view(s)
194
checked on 02-may-2024
Download(s)
191
checked on 02-may-2024