دورية أكاديمية
Genes and variants underlying human congenital lactic acidosis—from genetics to personalized treatment
| العنوان: | Genes and variants underlying human congenital lactic acidosis—from genetics to personalized treatment |
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| المؤلفون: | 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, Martín, Miguel Ángel, Desviat, Lourdes R., Ugarte, Magdalena, Pérez-Cerdá, Celia, Merinero, Begoña, Pérez, Belén, Rodríguez-Pombo, Pilar |
| المساهمون: | Fundación Isabel Gemio, Fundación "la Caixa", European Commission, Comunidad de Madrid, Ministerio de Economía y Competitividad (España) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | congenital lactic acidosis, mitochondrial dysfunction, metabolomics datasets, Clinical-exome sequencing, RNA analysis, antisense therapy for mitochondrial disorders, healthcare, mitochondrial morphology |
| الوصف: | 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). ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2077-0383 31683770 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; B2017/BMD3721; Publisher's version; https://doi.org/10.3390/jcm8111811Test; Sí; Journal of Clinical Medicine 8(11): 1811 (2019); http://hdl.handle.net/10261/195344Test; http://dx.doi.org/10.13039/100012818Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100003329Test |
| DOI: | 10.3390/jcm8111811 |
| DOI: | 10.13039/100012818 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100003329 |
| الإتاحة: | https://doi.org/10.3390/jcm8111811Test https://doi.org/10.13039/100012818Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/501100003329Test http://hdl.handle.net/10261/195344Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.43AD427C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20770383 31683770 |
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| DOI: | 10.3390/jcm8111811 |