RT Journal Article
T1 Genes and Variants Underlying Human Congenital Lactic Acidosis-From Genetics to Personalized Treatment.
A1 Bravo-Alonso, Irene
A1 Navarrete, Rosa
A1 Vega, Ana Isabel
A1 Ruíz-Sala, Pedro
A1 García Silva, María Teresa
A1 Martín-Hernández, Elena
A1 Quijada-Fraile, Pilar
A1 Belanger-Quintana, Amaya
A1 Stanescu, Sinziana
A1 Bueno, María
A1 Vitoria, Isidro
A1 Toledo, Laura
A1 Couce, María Luz
A1 García-Jiménez, Inmaculada
A1 Ramos-Ruiz, Ricardo
A1 Martín, Miguel Ángel
A1 Desviat, Lourdes R
A1 Ugarte, Magdalena
A1 Pérez-Cerdá, Celia
A1 Merinero, Begoña
A1 Pérez, Belén
A1 Rodríguez-Pombo, Pilar
K1 RNA analysis
K1 antisense therapy for mitochondrial disorders
K1 clinical-exome sequencing
K1 congenital lactic acidosis
K1 healthcare
K1 metabolomics datasets
K1 mitochondrial dysfunction
K1 mitochondrial morphology
AB 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.
SN 2077-0383
YR 2019
FD 2019-11-01
LK https://hdl.handle.net/10668/27441
UL https://hdl.handle.net/10668/27441
LA en
DS RISalud
RD Apr 6, 2025