Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina.
Inborn errors of metabolism (IEM) are monogenic defects with great phenotypic and genetic variability. The study of patients with clinical suspicion of IEM includes first-line biochemical studies (metabolites in biological fluids) that guide specific enzymatic and/or genetic analyses. This diagnosti...
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2023
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/42681 |
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I10-R327-article-42681 |
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Universidad Nacional de Córdoba |
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Revista de la Facultad de Ciencias Médicas de Córdoba |
| language |
Español |
| format |
Artículo revista |
| topic |
Exome sequencing inborn errors of metabolism molecular diagnosis Secuenciación exómica errores innatos del metabolismo diagnóstico molecular |
| spellingShingle |
Exome sequencing inborn errors of metabolism molecular diagnosis Secuenciación exómica errores innatos del metabolismo diagnóstico molecular Grosso, CL Angaroni, CI Becerra , AB Guelbert, GA Silvera Ruiz , SM Nicola, JP Motrich, R Laróvere, LE Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. |
| topic_facet |
Exome sequencing inborn errors of metabolism molecular diagnosis Secuenciación exómica errores innatos del metabolismo diagnóstico molecular |
| author |
Grosso, CL Angaroni, CI Becerra , AB Guelbert, GA Silvera Ruiz , SM Nicola, JP Motrich, R Laróvere, LE |
| author_facet |
Grosso, CL Angaroni, CI Becerra , AB Guelbert, GA Silvera Ruiz , SM Nicola, JP Motrich, R Laróvere, LE |
| author_sort |
Grosso, CL |
| title |
Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. |
| title_short |
Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. |
| title_full |
Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. |
| title_fullStr |
Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. |
| title_full_unstemmed |
Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. |
| title_sort |
application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the centro de estudio de las metabolopatías congénitas (cemeco) in córdoba, argentina. |
| description |
Inborn errors of metabolism (IEM) are monogenic defects with great phenotypic and genetic variability. The study of patients with clinical suspicion of IEM includes first-line biochemical studies (metabolites in biological fluids) that guide specific enzymatic and/or genetic analyses. This diagnostic strategy, from phenotype to genotype, is effective when the clinical characteristics are highly suggestive and associated with specific biomarkers. In contrast, in complex diseases that do not present typical biochemical alterations, exome sequencing appears to be an effective and promising diagnostic tool. The objective of this work is to show the first experience in CEMECO of the application of exome sequencing for the molecular diagnosis of EIM.
Exome sequencing was performed in 50 patients with clinical and/or biochemical suspicion of IEM studied at CEMECO (April-2022/March-2023). Genomic DNA was purified from whole blood by Roche MagNA, and sequencing and analysis of exome data were performed by 3billion company (South Korea). The identified variants were classified according to the consensus criteria of the American College of Medical Genetics and Genomics.
The overall diagnosis rate was 54% (27/50): 21/27 patients with IEM (10 with high clinical-biochemical suspicion and 11 with non-specific clinical-biochemical findings) and 6/27 individuals with other genetic diseases, not IEM. In 3 patients, 2 coexisting genetic diseases were detected and in another 3 incidental findings were identified in genes associated with risk factors. The IEM identified included: aminoacidopathies (33.3%), organic acidurias (19.0%), mitochondriopathies (19.0%), fatty acid β-oxidation defects (14.4%), disorders of vitamins and cofactors (9.5%) and urea cycle defects (4.8%). Forty-one different genetic variants corresponding to 23 genes were identified, classified as: pathogenic (53.7%), probably pathogenic (19.5%) and of uncertain significance (26.8%).
Exome sequencing is an effective methodology in the diagnosis of metabolic and neurogenetic diseases (specially in complex or unresolved cases) allowing personalized, predictive and/or preventive medicine. Exome sequencing has revolutionized clinical practice by changing the paradigm to “reverse genomic medicine”: from genotype to phenotype. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2023 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/42681 |
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I10-R327-article-426812023-10-19T21:19:59Z Application of exome sequencing in the molecular diagnosis of inborn errors of metabolism: first experience at the Centro de Estudio de las Metabolopatías Congénitas (CEMECO) in Córdoba, Argentina. Aplicación de secuenciación exómica en el diagnóstico molecular de errores innatos del metabolismo: primera experiencia en el Centro de Estudio de las Metabolopatías Congénitas (CEMECO) de Córdoba, Argentina Grosso, CL Angaroni, CI Becerra , AB Guelbert, GA Silvera Ruiz , SM Nicola, JP Motrich, R Laróvere, LE Exome sequencing inborn errors of metabolism molecular diagnosis Secuenciación exómica errores innatos del metabolismo diagnóstico molecular Inborn errors of metabolism (IEM) are monogenic defects with great phenotypic and genetic variability. The study of patients with clinical suspicion of IEM includes first-line biochemical studies (metabolites in biological fluids) that guide specific enzymatic and/or genetic analyses. This diagnostic strategy, from phenotype to genotype, is effective when the clinical characteristics are highly suggestive and associated with specific biomarkers. In contrast, in complex diseases that do not present typical biochemical alterations, exome sequencing appears to be an effective and promising diagnostic tool. The objective of this work is to show the first experience in CEMECO of the application of exome sequencing for the molecular diagnosis of EIM. Exome sequencing was performed in 50 patients with clinical and/or biochemical suspicion of IEM studied at CEMECO (April-2022/March-2023). Genomic DNA was purified from whole blood by Roche MagNA, and sequencing and analysis of exome data were performed by 3billion company (South Korea). The identified variants were classified according to the consensus criteria of the American College of Medical Genetics and Genomics. The overall diagnosis rate was 54% (27/50): 21/27 patients with IEM (10 with high clinical-biochemical suspicion and 11 with non-specific clinical-biochemical findings) and 6/27 individuals with other genetic diseases, not IEM. In 3 patients, 2 coexisting genetic diseases were detected and in another 3 incidental findings were identified in genes associated with risk factors. The IEM identified included: aminoacidopathies (33.3%), organic acidurias (19.0%), mitochondriopathies (19.0%), fatty acid β-oxidation defects (14.4%), disorders of vitamins and cofactors (9.5%) and urea cycle defects (4.8%). Forty-one different genetic variants corresponding to 23 genes were identified, classified as: pathogenic (53.7%), probably pathogenic (19.5%) and of uncertain significance (26.8%). Exome sequencing is an effective methodology in the diagnosis of metabolic and neurogenetic diseases (specially in complex or unresolved cases) allowing personalized, predictive and/or preventive medicine. Exome sequencing has revolutionized clinical practice by changing the paradigm to “reverse genomic medicine”: from genotype to phenotype. Los errores innatos del metabolismo (EIM) son defectos monogénicos con gran variabilidad fenotípica y genética. El estudio de pacientes con sospecha clínica de EIM incluye estudios bioquímicos de primera línea (metabolitos en fluidos biológicos) que orientan a análisis enzimáticos y/o genéticos específicos. Esta estrategia diagnóstica, del fenotipo al genotipo, es eficaz cuando las características clínicas son altamente sugestivas y asociadas a biomarcadores específicos. Por el contrario, en enfermedades complejas que no presentan alteraciones bioquímicas típicas, la secuenciación del exoma se presenta como una herramienta diagnóstica efectiva y promisoria. El objetivo de este trabajo es mostrar la primera experiencia en CEMECO de la aplicación de secuenciación exómica para el diagnóstico molecular de EIM en nuestro medio. Se realizó secuenciación exómica en 50 pacientes con sospecha clínica y/o bioquímica de EIM estudiados en CEMECO (abril-2022/marzo-2023). El ADN genómico fue purificado de sangre entera mediante Roche MagNA, y la secuenciación y el análisis de los datos exómicos fueron realizados por la empresa 3billion (Corea del Sur). Las variantes identificadas fueron clasificadas según criterios consenso del American College of Medical Genetics and Genomics. La tasa de diagnóstico global fue del 54% (27/50): 21/27 pacientes con EIM (10 con alta sospecha clínica-bioquímica y 11 con hallazgos clínicos-bioquímicos inespecíficos) y 6/27 individuos con otras enfermedades genéticas, no EIM. En 3 pacientes se detectaron 2 enfermedades genéticas coexistentes y en otros 3 se identificaron hallazgos incidentales en genes asociados a factores de riesgo. Los EIM identificados incluyeron: aminoacidopatías (33,3%), acidurias orgánicas (19,0%), mitocondriopatías (19,0%), defectos de la β-oxidación de ácidos grasos (14,4%), defectos de cofactores/vitaminas (9,5%) y defectos en el ciclo de la urea (4,8%). Se identificaron 41 variantes genéticas diferentes correspondientes a 23 genes, clasificadas como: patogénica (53,7%), probablemente patogénica (19,5%) y de significancia incierta (26,8%). La secuenciación exómica es una metodología eficaz en el diagnóstico de enfermedades metabólicas y neurogenéticas, especialmente en casos complejos o no resueltos, permitiendo, en algunos casos, un tratamiento personalizado, predictivo y/o preventivo. La secuenciación exómica ha revolucionado la práctica clínica cambiando el paradigma a una “medicina genómica inversa”: del genotipo al fenotipo. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2023-10-19 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/42681 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 80 (2023): Suplemento JIC XXIV Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 80 (2023): Suplemento JIC XXIV Revista da Faculdade de Ciências Médicas de Córdoba; v. 80 (2023): Suplemento JIC XXIV 1853-0605 0014-6722 spa https://revistas.unc.edu.ar/index.php/med/article/view/42681/42866 Derechos de autor 2023 Universidad Nacional de Córdoba http://creativecommons.org/licenses/by-nc/4.0 |