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

Loos, Mariana; Gómez, Gimena; Mayorga, Lía; Caraballo, Roberto; Eiroa, Hernán; Obregón, María Gabriela; Rugilo, Carlos; Lubieniecki, Fabiana; Taratuto, Ana Lía; Saccoliti, M.; Alonso, Cristina N.; Aráoz, Hilda Verónica

doi:10.1016/j.ymgmr.2021.100733

Cited by 3 publications

(9 citation statements)

References 52 publications

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“…In 20 years, among 902 children with a confirmed MD molecular diagnosis, we found 150 patients (16.7%) with an mtDNA pathogenic defect, similar to other pediatric cohort studies (14.4%–20.5%) [1–3] but unlike Loos et al (30%) [13]. Our data confirm mtDNA impairment is less frequent than nDNA defects in pediatric MDs.…”

Section: Discussionsupporting

confidence: 88%

“…Ocular motility alterations and/or ptosis were more frequent both at onset (17.3%) and during disease progression (33.3%) than previously reported [3, 13, 22, 23]. Vision loss was similarly more frequent than expected in mtDNA‐related MDs (22.6% at onset and 36.6% at follow‐up, vs. 12%–18.5% in literature) [7, 13, 22]. Although this symptom is part of the diagnostic criteria for some phenotypes (LHON, KSS, NARP), we also found it in other phenotypes (e.g., LS and MELAS, 24% and 14.2%, respectively).…”

Section: Discussionsupporting

confidence: 56%

“…Although SLSMDs are a common cause of adult MDs, accounting for approximately 16% of all adult mtDNA defects [50], prevalence is usually absent [7, 21] or lower in pediatric cohorts (8%–18%) [2, 13, 20]. In contrast, SLSMDs were frequent in our cohort (26.9%).…”

Section: Discussionmentioning

confidence: 63%

“…However, central respiratory involvement was quite rare (2.5% vs. 25.6% in Hu et al [22]). Ocular motility alterations and/or ptosis were more frequent both at onset (17.3%) and during disease progression (33.3%) than previously reported [3, 13, 22, 23]. Vision loss was similarly more frequent than expected in mtDNA‐related MDs (22.6% at onset and 36.6% at follow‐up, vs. 12%–18.5% in literature) [7, 13, 22].…”

Section: Discussionmentioning

confidence: 70%

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Phenotyping mitochondrial DNA‐related diseases in childhood: A cohort study of 150 patients

Ardissone

Ferrera

Lamperti

et al. 2023

Euro J of Neurology

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Background and purpose: Mitochondrial diseases (MDs) are heterogeneous disorders caused by mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) associated with specific syndromes. However, especially in childhood, patients often display heterogeneity. Several reports on the biochemical and molecular profiles in children have been published, but studies tend not to differentiate between mtDNA-and nDNA-associated diseases, and focus is often on a specific phenotype. Thus, large cohort studies specifically focusing on mtDNA defects in the pediatric population are lacking. Methods:We reviewed the clinical, metabolic, biochemical, and neuroimaging data of 150 patients with MDs due to mtDNA alterations collected at our neurological institute over the past 20 years.Results: mtDNA impairment is less frequent than nDNA impairment in pediatric MDs.Ocular involvement is extremely frequent in our cohort, as is classical Leber hereditary optic neuropathy, especially with onset before 12 years of age. Extraneurological manifestations and isolated myopathy appear to be rare, unlike adult phenotypes. Deep gray matter involvement, early disease onset, and specific phenotypes, such as Pearson syndrome and Leigh syndrome, represent unfavorable prognostic factors. Phenotypes related to single large scale mtDNA deletions appear to be very frequent in the pediatric population. Furthermore, we report for the first time an mtDNA pathogenic variant associated with cavitating leukodystrophy. Conclusions:We report on a large cohort of pediatric patients with mtDNA defects, adding new data on the phenotypical characterization of mtDNA defects and suggestions for diagnostic workup and therapeutic approach.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 70%

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Phenotyping mitochondrial DNA‐related diseases in childhood: A cohort study of 150 patients

Ardissone

Ferrera

Lamperti

et al. 2023

Euro J of Neurology

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“…To the best of our knowledge, only 1 patient with LHON from our country has been reported before, in a publication studying 27 patients with diverse pediatric mtDNA disorders [58], making the results of these 100 patients in our country the first report showing the prevalence of mutations for LHON patients in Argentina, and which includes mostly adult patients. The diagnostic algorithm, including the study of point mtDNA variants, was efficient and advantageous for this study, and even when the higher diagnostic yield of running whole mtDNA sequence analysis is proven, this test limited to frequent mutations resulted in a beneficial cost-effective study for routine analysis of patients in our country.…”

Section: Plos Onementioning

confidence: 94%

Mitochondrial DNA variants in a cohort from Argentina with suspected Leber’s hereditary optic neuropathy (LHON)

et al. 2023

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The present study investigates the spectrum and analysis of mitochondrial DNA (mtDNA) variants associated with Leber hereditary optic neuropathy (LHON) in an Argentinean cohort, analyzing 3 LHON-associated mitochondrial genes. In 32% of the cases, molecular confirmation of the diagnosis could be established, due to the identification of disease-causing variants. A total of 54 variants were observed in a cohort of 100 patients tested with direct sequencing analysis. The frequent causative mutations m.11778G>A in MT-ND4, m.3460G>A in MT-ND1, and m.14484T>C in MT-ND6 were identified in 28% of the cases of our cohort. Secondary mutations in this Argentinean LHON cohort were m.11253T>C p.Ile165Thr in MT-ND4, identified in three patients (3/100, 3%) and m.3395A>G p.Tyr30Cys in MT-ND1, in one of the patients studied (1%). This study shows, for the first time, the analysis of mtDNA variants in patients with a probable diagnosis of LHON in Argentina. Standard molecular methods are an effective first approach in order to achieve genetic diagnosis of the disease, leaving NGS tests for those patients with negative results.

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Phenotypes and genotypes of mitochondrial diseases with mtDNA variations in Chinese children: A multi-center study

et al. 2022

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

Cited by 3 publications

References 52 publications

Phenotyping mitochondrial DNA‐related diseases in childhood: A cohort study of 150 patients

Phenotyping mitochondrial DNA‐related diseases in childhood: A cohort study of 150 patients

Mitochondrial DNA variants in a cohort from Argentina with suspected Leber’s hereditary optic neuropathy (LHON)

Phenotypes and genotypes of mitochondrial diseases with mtDNA variations in Chinese children: A multi-center study

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