Neonatal encephalocardiomyopathy caused by mutations in VARS2
| Autor: | Thomas Meitinger, Sonja Budaeus, Tim M. Strom, Annette Seibt, Bader Alhaddad, Felix Distelmaier, Jörg Schaper, Holger Prokisch, Ertan Mayatepek, Tobias B. Haack, Fabian Baertling |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Mitochondrial encephalomyopathy Pathology medicine.medical_specialty Valine-tRNA Ligase Mitochondrial disease DNA Mutational Analysis Cardiomyopathy Biology Compound heterozygosity Corpus callosum Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience HLA Antigens Mitochondrial Encephalomyopathies medicine Humans Exome Exome sequencing Epilepsy Cardiomyopathy Hypertrophic medicine.disease VARS2 OXPHOS Aminoacyl tRNA synthtetas Hypoplasia 030104 developmental biology Mutation Neurology (clinical) Severe lactic acidosis |
| Zdroj: | Metab. Brain Dis. 32, 267-270 (2017) |
| ISSN: | 1573-7365 0885-7490 |
| DOI: | 10.1007/s11011-016-9890-2 |
| Popis: | VARS2 encodes a mitochondrial aminoacyl-tRNA-synthetase. Mutations in VARS2 have recently been identified as a cause of mitochondrial encephalomyopathy in three individuals. However, clinical information remained scarce. Exome sequencing lead us to identify compound heterozygous pathogenic VARS2 variants in a boy presenting with severe lactic acidosis, hypertrophic cardiomyopathy, epilepsy, and abnormalities on brain imaging including hypoplasia of corpus callosum and cerebellum as well as a massive lactate peak on MR-spectroscopy. Studies in patient-derived fibroblasts confirmed the functional relevance of the identified VARS2 variants. Our report expands the phenotypic spectrum associated with this rare mitochondrial defect, in that VARS2 deficiency may also cause severe neonatal presentations with cardiac involvement and structural brain abnormalities. |
| Databáze: | OpenAIRE |
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