Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm.
Congenital Glycosylation Disorders (CDG) are human genetic diseases (1: 20,000) due to the alteration in genes involved in the multiple pathways of glycoconjugates (glycoproteins, glycolipids, GPI anchors, among others). The clinical phenotype is multisystemic with a broad range of severity, even be...
| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
| Lenguaje: | Español |
| Publicado: |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2019
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| Materias: | |
| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/25894 |
| Aporte de: |
| id |
I10-R327-article-25894 |
|---|---|
| record_format |
ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
| repository_str |
R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| language |
Español |
| format |
Artículo revista |
| topic |
glycosylation algorithm for diagnose NGS NGS glicosilación IEF-Tf |
| spellingShingle |
glycosylation algorithm for diagnose NGS NGS glicosilación IEF-Tf Papazoglu , GM Cubilla, M Vega, A Pereyra , M Spécola, N Dodelson de Kremer , R Pérez, B Asteggiano, C Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. |
| topic_facet |
glycosylation algorithm for diagnose NGS NGS glicosilación IEF-Tf |
| author |
Papazoglu , GM Cubilla, M Vega, A Pereyra , M Spécola, N Dodelson de Kremer , R Pérez, B Asteggiano, C |
| author_facet |
Papazoglu , GM Cubilla, M Vega, A Pereyra , M Spécola, N Dodelson de Kremer , R Pérez, B Asteggiano, C |
| author_sort |
Papazoglu , GM |
| title |
Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. |
| title_short |
Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. |
| title_full |
Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. |
| title_fullStr |
Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. |
| title_full_unstemmed |
Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. |
| title_sort |
congenital disorders of glycosylation: successful implementation of mass sequencing in the diagnostic algorithm. |
| description |
Congenital Glycosylation Disorders (CDG) are human genetic diseases (1: 20,000) due to the alteration in genes involved in the multiple pathways of glycoconjugates (glycoproteins, glycolipids, GPI anchors, among others). The clinical phenotype is multisystemic with a broad range of severity, even being very serious with neonatal death. The diagnosis begins with the clinical suspicion and subsequent the study of serum transferrin (a N-glycoprotein) by the isoelectrofocusing technique (IEF-Tf) the most frequent test. There are more than 130 genes involved in these pathologies thus the algorithm for diagnose is complex and the synchronization of Mass Sequencing technology (NGS) combined with the biochemical analysis has allowed progress in the detection of new CDG patients.
The objective was to communicate the advances in the study of CDG through the use of NGS in Argentine patients.
A total of 240 individuals with clinical suspicion of CDG, derived from different medical centers during the 2015-2019 periods were studied. The inclusion criteria were at least three manifestations: axial hypotonia, mature delay, frequent infections, enteropathy, coagulopathy, cerebellar hypoplasia, congenital myasthenic syndrome or metabolic disease of unknown origin.
The study of serum Tf-IEF was carried out and subsequently in patients with altered patterns genomic DNA was obtained and massive sequencing done (NGS Illumina platform). Results: 4 altered Tf-IEF were identified, in 3 of them a nonsense variant not yet reported (c.753G> T; p.Arg251Leu) was detected in homozygosis in exon 2 of the ALG-2 gene (OMIM # 607906) (<1 / 1,000,000). Through in silico analysis, the mutation showed to be moderately pathogenic. The genetic variants found in a fourth patient do not correspond to genes associated with CDG (Tf-IEF altered by secondary causes).
Due to the large number of genes involved in the N-glycosylation pathway and the similarity in the clinical manifestations of these patients, the use of NGS combined with biochemical screening allow to improved the diagnosis of patients with CDG in our country. Together the detection of very rare CDG classes worldwide may possibly to describe new genes associated with CDG. CONICET-UCC-UNC. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2019 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/25894 |
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2024-09-03T21:01:16Z |
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I10-R327-article-258942024-08-27T18:26:35Z Congenital Disorders of Glycosylation: successful implementation of Mass Sequencing in the diagnostic algorithm. Desórdenes Congénitos de Glicosilación: utilidad de la Secuenciación Masiva en el algoritmo diagnóstico. Papazoglu , GM Cubilla, M Vega, A Pereyra , M Spécola, N Dodelson de Kremer , R Pérez, B Asteggiano, C glycosylation algorithm for diagnose NGS NGS glicosilación IEF-Tf Congenital Glycosylation Disorders (CDG) are human genetic diseases (1: 20,000) due to the alteration in genes involved in the multiple pathways of glycoconjugates (glycoproteins, glycolipids, GPI anchors, among others). The clinical phenotype is multisystemic with a broad range of severity, even being very serious with neonatal death. The diagnosis begins with the clinical suspicion and subsequent the study of serum transferrin (a N-glycoprotein) by the isoelectrofocusing technique (IEF-Tf) the most frequent test. There are more than 130 genes involved in these pathologies thus the algorithm for diagnose is complex and the synchronization of Mass Sequencing technology (NGS) combined with the biochemical analysis has allowed progress in the detection of new CDG patients. The objective was to communicate the advances in the study of CDG through the use of NGS in Argentine patients. A total of 240 individuals with clinical suspicion of CDG, derived from different medical centers during the 2015-2019 periods were studied. The inclusion criteria were at least three manifestations: axial hypotonia, mature delay, frequent infections, enteropathy, coagulopathy, cerebellar hypoplasia, congenital myasthenic syndrome or metabolic disease of unknown origin. The study of serum Tf-IEF was carried out and subsequently in patients with altered patterns genomic DNA was obtained and massive sequencing done (NGS Illumina platform). Results: 4 altered Tf-IEF were identified, in 3 of them a nonsense variant not yet reported (c.753G> T; p.Arg251Leu) was detected in homozygosis in exon 2 of the ALG-2 gene (OMIM # 607906) (<1 / 1,000,000). Through in silico analysis, the mutation showed to be moderately pathogenic. The genetic variants found in a fourth patient do not correspond to genes associated with CDG (Tf-IEF altered by secondary causes). Due to the large number of genes involved in the N-glycosylation pathway and the similarity in the clinical manifestations of these patients, the use of NGS combined with biochemical screening allow to improved the diagnosis of patients with CDG in our country. Together the detection of very rare CDG classes worldwide may possibly to describe new genes associated with CDG. CONICET-UCC-UNC. Los Desórdenes Congénitos de la Glicosilación (CDG) son enfermedades genéticas humanas (1:20.000) debidas a alteración en genes implicados en las múltiples vías de formación de glicoconjugados (glicoproteínas, glicolípidos, anclajes GPI, entre otros). El fenotipo clínico es multisistémico y de severidad variable, siendo incluso muy grave con muerte neonatal. El diagnóstico comienza con las sospecha clínica y posterior estudio de la N-glicoproteína sérica transferrina mediante la técnica de isoelectroenfocado (IEF-Tf). Debido a que existen más de 130 genes involucrados en estas patologías, el algoritmo de estudio es complejo y la incorporación de tecnología de Secuenciación Masiva (NGS) combinada con el análisis bioquímico, han permitido avanzar en la detección de nuevos pacientes. El objetivo del trabajo fue comunicar los avances en el estudio de CDG mediante el uso de NGS en pacientes argentinos. Fueron incluidos 240 individuos con sospecha clínica de CDG, derivados de diferentes centros médicos del país durante el periodo 2015 – 2019. Los criterios de inclusión fueron al menos tres manifestaciones: hipotonía axial, retraso madurativo, infecciones frecuentes, enteropatía, coagulopatia, hipoplasia cerebelo, síndrome miasténico congénito o metabolopatía de origen desconocido. Se realizó el estudio de Tf-IEF en suero y posteriormente en pacientes con patrones alterado la obtención de ADN genómico y secuenciación masiva (NGS plataforma Illumina). Resultados: se identificaron 4 Tf-IEF alterados, en 3 de ellos se detectó por NGS, una variante missense aun no reportada (c.753G>T; p.Arg251Leu) en homocigosis en el exón 2 del gen ALG-2 (OMIM # 607906) (<1 / 1.000.000). Mediante análisis in silico, se observó que la mutación sería moderadamente patogénica. Las variantes genéticas encontradas en un cuarto paciente no se corresponden con genes asociados a CDG (Tf-IEF alterado por causas secundarias). Debido a la gran cantidad de genes involucrados en la vía de N-glicosilación y a la similitud en las manifestaciones clínicas de estos pacientes, el uso de NGS combinado con el screening bioquímico, han permitido acelerar el diagnostico de pacientes con CDG en nuestro país y la detección de clases de CDG muy poco frecuentes a nivel mundial o eventualmente nuevos genes asociados a las mismas. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2019-10-22 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/25894 Revista de la Facultad de Ciencias Médicas de Córdoba.; 2019: Suplemento JIC XX Revista de la Facultad de Ciencias Médicas de Córdoba; 2019: Suplemento JIC XX Revista da Faculdade de Ciências Médicas de Córdoba; 2019: Suplemento JIC XX 1853-0605 0014-6722 10.31053/1853.0605.v76.nSuplemento spa https://revistas.unc.edu.ar/index.php/med/article/view/25894/27714 Derechos de autor 2019 Universidad Nacional de Córdoba https://creativecommons.org/licenses/by-nc/4.0 |