Novel (ovario) leukodystrophy related to AARS2 mutations
| العنوان: | Novel (ovario) leukodystrophy related to AARS2 mutations |
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| المؤلفون: | Thomas Meitinger, Nicole I. Wolf, Tim M. Strom, Raphael Schiffmann, Alison Colley, Enrico Baruffini, Eline M. Hamilton, Cristina Dallabona, Adeline Vanderver, Ileana Ferrero, Daniele Ghezzi, Helena Rocha, Truus E.M. Abbink, Marjo S. van der Knaap, Katrin Õunap, Tobias B. Haack, Massimo Zeviani, Costanza Lamperti, Laura Melchionda, Gajja S. Salomons, Caterina Mariotti, Ettore Salsano, Mario Savoiardo, Kim Chapman, Sietske H. Kevelam, Holger Prokisch, Lee-Jun C. Wong, Daria Diodato |
| المساهمون: | Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Laboratory Medicine, Pediatric surgery, NCA - Brain mechanisms in health and disease, Other departments |
| المصدر: | Neurology 82, 2063-2071 (2014) Neurology, 82(23), 2063-2071. American Academy of Neurology Neurology, 82(23), 2063-2071. Lippincott Williams and Wilkins Dallabona, C, Diodato, D, Kevelam, S H, Haack, T B, Wong, L J, Salomons, G S, Baruffini, E, Melchionda, L, Mariotti, C, Strom, T M, Meitinger, T, Prokisch, H, Chapman, K, Colley, A, Rocha, H, Ounap, K, Schiffmann, R, Salsano, E, Savoiardo, M, Hamilton, E M C, Abbink, G E M, Wolf, N I, Ferrero, I, Lamperti, C, Zeviani, M, Vanderver, A, Ghezzi, D & van der Knaap, M S 2014, ' Novel (ovario) leukodystrophy related to AARS2 mutations ', Neurology, vol. 82, no. 23, pp. 2063-2071 . https://doi.org/10.1212/WNL.0000000000000497Test |
| بيانات النشر: | Lippincott Williams & Wilkins, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Pathology, medicine.medical_specialty, Ataxia, Adolescent, Cardiomyopathy, Biology, Primary Ovarian Insufficiency, Compound heterozygosity, medicine.disease_cause, Article, Leukoencephalopathy, Young Adult, Atrophy, SDG 3 - Good Health and Well-being, Leukoencephalopathies, medicine, Humans, Cognitive decline, Alanine-tRNA Ligase, Cognition Disorders, Exons, Female, Magnetic Resonance Imaging, Muscle Spasticity, Mutation, Phenotype, Leukodystrophy, medicine.disease, Neurology (clinical), medicine.symptom |
| الوصف: | Objectives: The study was focused on leukoencephalopathies of unknown cause in order to define a novel, homogeneous phenotype suggestive of a common genetic defect, based on clinical and MRI findings, and to identify the causal genetic defect shared by patients with this phenotype. Methods: Independent next-generation exome-sequencing studies were performed in 2 unrelated patients with a leukoencephalopathy. MRI findings in these patients were compared with available MRIs in a database of unclassified leukoencephalopathies; 11 patients with similar MRI abnormalities were selected. Clinical and MRI findings were investigated. Results: Next-generation sequencing revealed compound heterozygous mutations in AARS2 encoding mitochondrial alanyl-tRNA synthetase in both patients. Functional studies in yeast confirmed the pathogenicity of the mutations in one patient. Sanger sequencing revealed AARS2 mutations in 4 of the 11 selected patients. The 6 patients with AARS2 mutations had childhoodto adulthood-onset signs of neurologic deterioration consisting of ataxia, spasticity, and cognitive decline with features of frontal lobe dysfunction. MRIs showed a leukoencephalopathy with striking involvement of left-right connections, descending tracts, and cerebellar atrophy. All female patients had ovarian failure. None of the patients had signs of a cardiomyopathy. Conclusions: Mutations in AARS2 have been found in a severe form of infantile cardiomyopathy in 2 families. We present 6 patients with a new phenotype caused by AARS2 mutations, characterized by leukoencephalopathy and, in female patients, ovarian failure, indicating that the phenotypic spectrum associated with AARS2 variants is much wider than previously reported. © 2014 American Academy of Neurology. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0028-3878 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55193fd95af1d17d800cb702813c2884Test https://europepmc.org/articles/PMC4118500Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....55193fd95af1d17d800cb702813c2884 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00283878 |
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