TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

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dc.contributor.authorBallestrini, Simona
dc.contributor.authorMathieu, Milh
dc.contributor.authorCastiglioni, Claudia
dc.contributor.authorLüthy, Kevin
dc.contributor.authorFinelli, Mattea
dc.contributor.authorVerstreken, Patrik
dc.contributor.authorCardon, Aaron
dc.contributor.authorGnidovec, Barbara
dc.contributor.authorHolder, Lloyd
dc.contributor.authorLesca, Gaetan
dc.contributor.authorMancardi, María
dc.contributor.authorPoulat, Anne
dc.contributor.authorRepetto, Gabriela
dc.contributor.authoret al.
dc.date.accessioned2017-01-04T15:12:33Z
dc.date.available2017-01-04T15:12:33Z
dc.date.issued2016
dc.descriptionCentro e Genética y Genómica
dc.description.abstractOBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. METHODS: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). RESULTS: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. CONCLUSIONS: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.
dc.identifier.citationNeurology, July 2016, vol.87, n°1,p.77-85
dc.identifier.urihttp://hdl.handle.net/11447/919
dc.identifier.urihttp://dx.doi.org/10.1212/WNL.0000000000002807
dc.language.isoen_US
dc.publisherLippincott Williams & Wilkins
dc.subjectInfantile myoclonic epilepsy
dc.subjectEpilepsy
dc.subjectDoors syndrome
dc.subjectHearing loss
dc.subjectNeurodegeneration
dc.titleTBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.
dc.typeArtículo

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