Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients

Autores
Loos, Mariana Amina; Gomez, Gimena; Mayorga, Lía; Caraballo, Roberto Horacio; Eiroa, Hernán Diego; Obregon, María Gabriela; Rugilo, Carlos; Lubieniecki, Fabiana; Taratuto, Ana Lía; Saccoliti, María; Alonso, Cristina Noemí; Aráoz, Hilda Verónica
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases. Methods: Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. Results: Patients were 18 females and 9 males, with ages at onset ranging from 1 week to 14 years (median = 4 years). The clinical phenotypes were: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 11), Leigh syndrome (n = 5), Kearns-Sayre syndrome (n = 3), Chronic Progressive External Ophthalmoplegia (n = 2), Leber hereditary optic neuropathy (n = 2), myoclonic epilepsy associated with ragged-red fibers (n = 1) and reversible infantile myopathy with cytochrome-C oxidase deficiency (n = 3). Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK. Other point variants were found in complex I subunits, like MT-ND6, MT-ND4, MT-ND5; or in MT-ATP6. The m.13513G > A variant in MT-ND5 and the m.9185 T > C variant in MT-ATP6 were apparently de novo. The rest of the patients presented large scale-rearrangements, either the ?common? deletion or a larger deletion. Conclusions: This study highlights the clinical and genetic heterogeneity of pediatric mtDNA disorders. All the cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.
Fil: Loos, Mariana Amina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gomez, Gimena. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Mayorga, Lía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Caraballo, Roberto Horacio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Eiroa, Hernán Diego. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Obregon, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Rugilo, Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Taratuto, Ana Lía. No especifíca;
Fil: Saccoliti, María. No especifíca;
Fil: Alonso, Cristina Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aráoz, Hilda Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Materia
LEIGH SYNDROME
MELAS
MITOCHONDRIAL DISEASES
MITOCHONDRIAL DNA
MOLECULAR DIAGNOSIS
PEDIATRICS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/157744
Acceder
id CONICETDig_eb1a6a8d9bea1d719f56974b1e283153
oai_identifier_str oai:ri.conicet.gov.ar:11336/157744
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patientsLoos, Mariana AminaGomez, GimenaMayorga, LíaCaraballo, Roberto HoracioEiroa, Hernán DiegoObregon, María GabrielaRugilo, CarlosLubieniecki, FabianaTaratuto, Ana LíaSaccoliti, MaríaAlonso, Cristina NoemíAráoz, Hilda VerónicaLEIGH SYNDROMEMELASMITOCHONDRIAL DISEASESMITOCHONDRIAL DNAMOLECULAR DIAGNOSISPEDIATRICShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objective: To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases. Methods: Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. Results: Patients were 18 females and 9 males, with ages at onset ranging from 1 week to 14 years (median = 4 years). The clinical phenotypes were: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 11), Leigh syndrome (n = 5), Kearns-Sayre syndrome (n = 3), Chronic Progressive External Ophthalmoplegia (n = 2), Leber hereditary optic neuropathy (n = 2), myoclonic epilepsy associated with ragged-red fibers (n = 1) and reversible infantile myopathy with cytochrome-C oxidase deficiency (n = 3). Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK. Other point variants were found in complex I subunits, like MT-ND6, MT-ND4, MT-ND5; or in MT-ATP6. The m.13513G > A variant in MT-ND5 and the m.9185 T > C variant in MT-ATP6 were apparently de novo. The rest of the patients presented large scale-rearrangements, either the ?common? deletion or a larger deletion. Conclusions: This study highlights the clinical and genetic heterogeneity of pediatric mtDNA disorders. All the cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.Fil: Loos, Mariana Amina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gomez, Gimena. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Mayorga, Lía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Caraballo, Roberto Horacio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Eiroa, Hernán Diego. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Obregon, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Rugilo, Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Taratuto, Ana Lía. No especifíca;Fil: Saccoliti, María. No especifíca;Fil: Alonso, Cristina Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Aráoz, Hilda Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaElsevier Inc2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/157744Loos, Mariana Amina; Gomez, Gimena; Mayorga, Lía; Caraballo, Roberto Horacio; Eiroa, Hernán Diego; et al.; Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients; Elsevier Inc; Molecular Genetics and Metabolism Reports; 27; 6-2021; 1-72214-4269CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgmr.2021.100733info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:46:55Zoai:ri.conicet.gov.ar:11336/157744instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:46:56.165CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
title Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
spellingShingle Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
Loos, Mariana Amina
LEIGH SYNDROME
MELAS
MITOCHONDRIAL DISEASES
MITOCHONDRIAL DNA
MOLECULAR DIAGNOSIS
PEDIATRICS
title_short Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
title_full Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
title_fullStr Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
title_full_unstemmed Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
title_sort Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients
dc.creator.none.fl_str_mv Loos, Mariana Amina
Gomez, Gimena
Mayorga, Lía
Caraballo, Roberto Horacio
Eiroa, Hernán Diego
Obregon, María Gabriela
Rugilo, Carlos
Lubieniecki, Fabiana
Taratuto, Ana Lía
Saccoliti, María
Alonso, Cristina Noemí
Aráoz, Hilda Verónica
author Loos, Mariana Amina
author_facet Loos, Mariana Amina
Gomez, Gimena
Mayorga, Lía
Caraballo, Roberto Horacio
Eiroa, Hernán Diego
Obregon, María Gabriela
Rugilo, Carlos
Lubieniecki, Fabiana
Taratuto, Ana Lía
Saccoliti, María
Alonso, Cristina Noemí
Aráoz, Hilda Verónica
author_role author
author2 Gomez, Gimena
Mayorga, Lía
Caraballo, Roberto Horacio
Eiroa, Hernán Diego
Obregon, María Gabriela
Rugilo, Carlos
Lubieniecki, Fabiana
Taratuto, Ana Lía
Saccoliti, María
Alonso, Cristina Noemí
Aráoz, Hilda Verónica
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LEIGH SYNDROME
MELAS
MITOCHONDRIAL DISEASES
MITOCHONDRIAL DNA
MOLECULAR DIAGNOSIS
PEDIATRICS
topic LEIGH SYNDROME
MELAS
MITOCHONDRIAL DISEASES
MITOCHONDRIAL DNA
MOLECULAR DIAGNOSIS
PEDIATRICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases. Methods: Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. Results: Patients were 18 females and 9 males, with ages at onset ranging from 1 week to 14 years (median = 4 years). The clinical phenotypes were: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 11), Leigh syndrome (n = 5), Kearns-Sayre syndrome (n = 3), Chronic Progressive External Ophthalmoplegia (n = 2), Leber hereditary optic neuropathy (n = 2), myoclonic epilepsy associated with ragged-red fibers (n = 1) and reversible infantile myopathy with cytochrome-C oxidase deficiency (n = 3). Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK. Other point variants were found in complex I subunits, like MT-ND6, MT-ND4, MT-ND5; or in MT-ATP6. The m.13513G > A variant in MT-ND5 and the m.9185 T > C variant in MT-ATP6 were apparently de novo. The rest of the patients presented large scale-rearrangements, either the ?common? deletion or a larger deletion. Conclusions: This study highlights the clinical and genetic heterogeneity of pediatric mtDNA disorders. All the cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.
Fil: Loos, Mariana Amina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gomez, Gimena. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Mayorga, Lía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Caraballo, Roberto Horacio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Eiroa, Hernán Diego. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Obregon, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Rugilo, Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Taratuto, Ana Lía. No especifíca;
Fil: Saccoliti, María. No especifíca;
Fil: Alonso, Cristina Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aráoz, Hilda Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
description Objective: To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases. Methods: Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. Results: Patients were 18 females and 9 males, with ages at onset ranging from 1 week to 14 years (median = 4 years). The clinical phenotypes were: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 11), Leigh syndrome (n = 5), Kearns-Sayre syndrome (n = 3), Chronic Progressive External Ophthalmoplegia (n = 2), Leber hereditary optic neuropathy (n = 2), myoclonic epilepsy associated with ragged-red fibers (n = 1) and reversible infantile myopathy with cytochrome-C oxidase deficiency (n = 3). Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK. Other point variants were found in complex I subunits, like MT-ND6, MT-ND4, MT-ND5; or in MT-ATP6. The m.13513G > A variant in MT-ND5 and the m.9185 T > C variant in MT-ATP6 were apparently de novo. The rest of the patients presented large scale-rearrangements, either the ?common? deletion or a larger deletion. Conclusions: This study highlights the clinical and genetic heterogeneity of pediatric mtDNA disorders. All the cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.
publishDate 2021
dc.date.none.fl_str_mv 2021-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/157744
Loos, Mariana Amina; Gomez, Gimena; Mayorga, Lía; Caraballo, Roberto Horacio; Eiroa, Hernán Diego; et al.; Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients; Elsevier Inc; Molecular Genetics and Metabolism Reports; 27; 6-2021; 1-7
2214-4269
CONICET Digital
CONICET
url http://hdl.handle.net/11336/157744
identifier_str_mv Loos, Mariana Amina; Gomez, Gimena; Mayorga, Lía; Caraballo, Roberto Horacio; Eiroa, Hernán Diego; et al.; Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients; Elsevier Inc; Molecular Genetics and Metabolism Reports; 27; 6-2021; 1-7
2214-4269
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgmr.2021.100733
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc
publisher.none.fl_str_mv Elsevier Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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