Early and lethal neurodegeneration with myasthenic and myopathic features:A new ALG14-CDG
| Autor: | Richard J. Rodenburg, Rudolf Korinthenberg, Lauren Brady, David Schorling, Dirk Lefeber, Clemens R. Müller, Carsten G. Bönnemann, Marcus Krüger, Marjo S. van der Knaap, Marianna Bugiani, Mark A. Tarnopolsky, Jan Kirschner, Simone Rost, Maria de los Angeles Beytía |
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| Přispěvatelé: | Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Amsterdam Reproduction & Development (AR&D), Pediatric surgery |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Severe muscular hypotonia Autopsy N-Acetylglucosaminyltransferases medicine.disease_cause Article 03 medical and health sciences Epilepsy Congenital Disorders of Glycosylation Fatal Outcome 0302 clinical medicine medicine Humans Cerebrum Exome sequencing Cerebral atrophy Mutation Muscle Weakness Muscle biopsy medicine.diagnostic_test business.industry Neurodegeneration Infant Neurodegenerative Diseases Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Syndrome Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] medicine.disease Pedigree Phenotype 030104 developmental biology Female Neurology (clinical) Atrophy business 030217 neurology & neurosurgery |
| Zdroj: | Schorling, D C, Rost, S, Lefeber, DI J, Brady, L, Müller, C R, Korinthenberg, R, Tarnopolsky, M, Bönnemann, C G, Rodenburg, R J, Bugiani, M, Beytia, M, Krüger, M, Van Der Knaap, M & Kirschner, J 2017, ' Early and lethal neurodegeneration with myasthenic and myopathic features : A new ALG14-CDG ', Neurology, vol. 89, no. 7, pp. 657-664 . https://doi.org/10.1212/WNL.0000000000004234 Neurology, 89, 657-664 Neurology, 89(7), 657-664. Lippincott Williams and Wilkins Neurology, 89, 7, pp. 657-664 |
| ISSN: | 0028-3878 |
| DOI: | 10.1212/WNL.0000000000004234 |
| Popis: | Objective:To describe the presentation and identify the cause of a new clinical phenotype, characterized by early severe neurodegeneration with myopathic and myasthenic features.Methods:This case study of 5 patients from 3 families includes clinical phenotype, serial MRI, electrophysiologic testing, muscle biopsy, and full autopsy. Genetic workup included whole exome sequencing and segregation analysis of the likely causal mutation.Results:All 5 patients showed severe muscular hypotonia, progressive cerebral atrophy, and therapy-refractory epilepsy. Three patients had congenital contractures. All patients died during their first year of life. In 2 of our patients, electrophysiologic testing showed abnormal decrement, but treatment with pyridostigmine led only to temporary improvement. Causative mutations in ALG14 were identified in all patients. The mutation c.220 G>A (p.Asp74Asn) was homozygous in 2 patients and heterozygous in the other 3 patients. Additional heterozygous mutations were c.422T>G (p.Val141Gly) and c.326G>A (p.Arg109Gln). In all cases, parents were found to be heterozygous carriers. None of the identified variants has been described previously.Conclusions:We report a genetic syndrome combining myasthenic features and severe neurodegeneration with therapy-refractory epilepsy. The underlying cause is a glycosylation defect due to mutations in ALG14. These cases broaden the phenotypic spectrum associated with ALG14 congenital disorders of glycosylation as previously only isolated myasthenia has been described. |
| Databáze: | OpenAIRE |
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