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http://purl.uniprot.org/citations/28733338http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28733338http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28733338http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.org/dc/terms/identifier"doi:10.1212/wnl.0000000000004234"xsd:string
http://purl.uniprot.org/citations/28733338http://purl.org/dc/terms/identifier"doi:10.1212/wnl.0000000000004234"xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Krueger M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Krueger M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Rodenburg R.J."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Rodenburg R.J."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Brady L."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Brady L."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Tarnopolsky M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Tarnopolsky M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Boennemann C.G."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Boennemann C.G."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Kirschner J."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Kirschner J."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Beytia M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Beytia M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Bugiani M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Bugiani M."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Korinthenberg R."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Korinthenberg R."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Lefeber D.J."xsd:string
http://purl.uniprot.org/citations/28733338http://purl.uniprot.org/core/author"Lefeber D.J."xsd:string
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