Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant
| Autor: | Isabel Alonso, Mariana Adrião, Elisa Leão Teles, Miguel Leão, Esmeralda Rodrigues, Margarida Ayres Basto, Laura Vilarinho, Mafalda Sampaio, Sandra Pereira |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetics Mitochondrial Encephalopathy RNA Mitochondrial diseases Oxidative phosphorylation VARS2 gene Biology Article Doenças Genéticas Transfer 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Mitochondrial respiratory chain Exome Sequencing Mitochondrial encephalopathy Missense mutation Amino Acyl Gene Severe Epileptic Encephalopathy 030217 neurology & neurosurgery Exome sequencing |
| Zdroj: | JIMD Reports ISBN: 9783662583647 |
| Popis: | Research report Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226392/ Introduction: Combined oxidative phosphorylation deficiency 20 (COXPD20) is a mitochondrial respiratory chain complex (RC) disorder, caused by disease-causing variants in the VARS2 gene, which encodes a mitochondrial aminoacyl-tRNA synthetase. Here we describe a patient with fatal mitochondrial encephalopathy caused by a homozygous VARS2 gene missense variant. Case Report: We report the case of a girl, the first child of non-consanguineous and healthy parents, born from an uneventful term pregnancy, who presented, in the neonatal period, major hypotonia and microcephaly. At 4 months of age she showed poor eye contact, nystagmus, global psychomotor development delay and failure to thrive, without dysmorphic features. Focal seizures started at 24 months which evolved to a severe epileptic encephalopathy and finally to super refractory status epilepticus, leading to her death at 28 months of age. Etiologic investigation encompassing metabolic and genetic causes failed to disclose a diagnosis. Post-mortem exome sequencing allowed the identification of a pathogenic variant in VARS2 gene in the homozygous state (c.1100C > T, p.Thr367Ile) in the patient, inherited from her heterozygous parents, leading to the diagnosis of COXPD2. Conclusion: To the best of our knowledge, this is the fifth case described in the literature of a child with disease-causing variant in VARS2. With this report we expand the knowledge about the phenotype associated with this very rare mitochondrial defect, further emphasizing the use of exome sequencing as a very powerful diagnostic tool. info:eu-repo/semantics/publishedVersion |
| Databáze: | OpenAIRE |
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