Genes and Variants Underlying Human Congenital Lactic Acidosis-From Genetics to Personalized Treatment
| Autor: | Magdalena Ugarte, Elena Martín-Hernández, Belén Pérez, Amaya Belanger-Quintana, Lourdes R. Desviat, Inmaculada García-Jiménez, Isidro Vitoria, Ricardo Ramos-Ruiz, Rosa Navarrete, Celia Pérez-Cerdá, Pilar Quijada-Fraile, María A. Bueno, Laura Toledo, María Teresa García Silva, Sinziana Stanescu, Ana I. Vega, Begoña Merinero, Pilar Rodríguez-Pombo, Irene Bravo-Alonso, Pedro Ruiz-Sala, Miguel Martín, María L. Couce |
|---|---|
| Přispěvatelé: | Fundación Isabel Gemio, Fundación 'la Caixa', European Commission, Comunidad de Madrid, Ministerio de Economía y Competitividad (España), UAM. Departamento de Biología Molecular |
| Rok vydání: | 2019 |
| Předmět: |
Mitochondrial DNA
Antisense therapy for mitochondrial disorders Clinical-exome sequencing Congenital lactic acidosis Healthcare Metabolomics datasets Mitochondrial dysfunction Mitochondrial morphology RNA analysis metabolomics datasets government.form_of_government congenital lactic acidosis mitochondrial dysfunction clinical-exome sequencing antisense therapy for mitochondrial disorders healthcare mitochondrial morphology lcsh:Medicine Computational biology Genetic analysis DNA sequencing Article 03 medical and health sciences Medicine Allele Gene Exome sequencing 030304 developmental biology Antisense therapy 0303 health sciences business.industry 030305 genetics & heredity lcsh:R General Medicine Biología y Biomedicina / Biología government business RNA analysis antisense therapy for mitochondrial disorders clinical-exome sequencing congenital lactic acidosis healthcare metabolomics datasets mitochondrial dysfunction mitochondrial morphology |
| Zdroj: | Journal of Clinical Medicine Journal of Clinical Medicine, Vol 8, Iss 11, p 1811 (2019) Journal of Clinical Medicine; Volume 8; Issue 11; Pages: 1811 Digital.CSIC. Repositorio Institucional del CSIC instname Journal of clinical medicine r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe |
| ISSN: | 2077-0383 |
| Popis: | 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 GFM1 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. This research was funded in part by Fundación Isabel Gemio, Fundación La Caixa (LCF/PR/PR16/11110018); Spanish Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) PI16/00573 and Regional Government of Madrid (CAM, B2017/BMD3721). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|