Expanding phenotype of mitochondrial depletion syndrome in association with TWNK mutations |
| |
| Affiliation: | 1. Department of Pediatric Neurology, Arabkir Medical Center, 30 Mamikonyants str., 0014 Yerevan, Armenia;2. Department of Pediatrics, Yerevan State Medical University, 2 Koryun str., 0025 Yerevan, Armenia;3. Department of Pediatric Neurology, University Children''s Hospital, 75, Steinwiesstrasse, 8032 Zurich, Switzerland;1. Complex Motor Disorder Service, Evelina London Children''s Hospital, Guy''s and St Thomas'' NHS Foundation Trust, Floor 2 Beckett House, Lambeth Palace Road, London, SE1 7EU, United Kingdom;2. F. Hoffmann-La Roche Ltd, Basel, Switzerland;3. King''s College London, Institute of Psychiatry, Psychology and Neurosciences, Psychology Department, London, SE5 8AF, United Kingdom;9. Child Neuropsychiatry Unit, Spedali Civili, Brescia, Italy;10. Genomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy;11. Child Neuropsychiatry Unit, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy;12. Department of Neurovascular Genetics, Hôpital Lariboisière, Paris, France;13. Neuroradiology Unit, S.S Neuroradiologia Pediatrica, Spedali Civili, Brescia, Italy;14. Radiology Institute, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy;15. Obstetrics and Gynecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy;p. Laboratory of Neurogenetics, Pediatric Neurology Unit, A. Meyer Children''s Hospital, Florence, Italy;q. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy;r. Medical Genetics, University of Pavia, Pavia, Italy;1. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy;2. Department of Neuroradiology, IRCCS Mondino Foundation, Pavia, Italy;3. Neuroradiology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy;4. Child Neurology Unit, V. Buzzi Children''s Hospital, Milan, Italy;5. Genomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy;6. Child Neuropsychiatry Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy;7. Medical Genetics, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy;8. Child and Adolescence Neurology Unit, IRCCS Mondino Foundation, Pavia, Italy;1. Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel;2. The Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;3. Obstetrics and Gynecology Ultrasound Unit in the Department of Obstetrics and Gynecology at Rambam Health Care Campus, Israel;4. Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;5. Department of Pediatrics, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel;1. The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, G51 4TF, UK;2. School of Medicine, University of Glasgow, Glasgow, G12 8QQ, UK |
| |
| Abstract: | Mitochondrial DNA depletion syndromes (MDS) are a group of clinically and genetically heterogeneous autosomal recessive disorders characterized by a reduction of mtDNA. We report two siblings of Armenian origin with early onset neurodegenerative disease characterized by encephalopathy, severe hypotonia, facial dyskinetic movements, abnormal eye movements, severe failure to thrive, and abnormal renal and hepatic function. Sanger sequencing confirmed two variants in the C10orf2 gene (TWNK) and indicated a diagnosis of MDS. Our recent observation confirms that nephrocalcinosis and proximal tubulopathy can be a part of a clinical picture of MDS associated with TWNK mutations and document peculiar ocular and orobuccolingual dyskinesias. Wrist myoclonia and tongue tremor were new clinical features in our patients. We suggest that the above-mentioned clinical constellation could potentially provide the basis for the diagnosis of MDS. |
| |
| Keywords: | Mitochondrial diseases Mitochondrial depletion syndromes Renal tubulopathy |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
