The diagnostic approach to mitochondrial disorders in children in the era of next-generation sequencing: A 4-year cohort study
| Autor: | Claudio Bruno, Giorgia Bruno, Annarita Ferrari, Federico Sicca, Lucia Ruggiero, Roberta Battini, Daniele Orsucci, Renzo Guerrini, M. Alice Donati, Francesca Pochiero, Anna Rubegni, Martino Montomoli, Francesco Mari, Deborah Tolomeo, Chiara Fiorillo, Claudia Nesti, Simone Sampaolo, Filippo M. Santorelli, Denise Cassandrini, Stefano Doccini, Elena Procopio, Jacopo Baldacci, Chiara Ticci, Simona Fiori |
|---|---|
| Přispěvatelé: | Tolomeo, D., Orsucci, D., Nesti, C., Baldacci, J., Battini, R., Bruno, C., Bruno, G., Cassandrini, D., Doccini, S., Donati, M. A., Ferrari, A., Fiori, S., Fiorillo, C., Guerrini, R., Mari, F., Montomoli, M., Pochiero, F., Procopio, E., Ruggiero, L., Sampaolo, S., Sicca, F., Ticci, C., Rubegni, A., Santorelli, F. M. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Diagnostic approach Mitochondrial DNA NDNA Mitochondrial disease MtDNA Bioinformatics Article DNA sequencing 03 medical and health sciences 0302 clinical medicine Genotype Basal ganglia Mitochondrial disorders MRI Muscle biopsy Next-generation sequencing Medicine Medical diagnosis business.industry Genetic heterogeneity General Medicine medicine.disease Mitochondrial disorder 030104 developmental biology diagnostic approach mitochondrial disorders next-generation sequencing mtDNA nDNA muscle biopsy basal ganglia Cohort business 030217 neurology & neurosurgery Cohort study |
| Zdroj: | Journal of Clinical Medicine; Volume 10; Issue 15; Pages: 3222 Journal of Clinical Medicine, Vol 10, Iss 3222, p 3222 (2021) Journal of Clinical Medicine |
| Popis: | Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new “genotype first” approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|