Dataset Information

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

ABSTRACT:

Objective

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.

SUBMITTER: Balestrini S

PROVIDER: S-EPMC4932231 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Balestrini Simona S Milh Mathieu M Castiglioni Claudia C Lüthy Kevin K Finelli Mattea J MJ Verstreken Patrik P Cardon Aaron A Stražišar Barbara Gnidovec BG Holder J Lloyd JL Lesca Gaetan G Mancardi Maria M MM Poulat Anne L AL Repetto Gabriela M GM Banka Siddharth S Bilo Leonilda L Birkeland Laura E LE Bosch Friedrich F Brockmann Knut K Cross J Helen JH Doummar Diane D Félix Temis M TM Giuliano Fabienne F Hori Mutsuki M Hüning Irina I Kayserili Hulia H Kini Usha U Lees Melissa M MM Meenakshi Girish G Mewasingh Leena L Pagnamenta Alistair T AT Peluso Silvio S Mey Antje A Rice Gregory M GM Rosenfeld Jill A JA Taylor Jenny C JC Troester Matthew M MM Stanley Christine M CM Ville Dorothee D Walkiewicz Magdalena M Falace Antonio A Fassio Anna A Lemke Johannes R JR Biskup Saskia S Tardif Jessica J Ajeawung Norbert F NF Tolun Aslihan A Corbett Mark M Gecz Jozef J Afawi Zaid Z Howell Katherine B KB Oliver Karen L KL Berkovic Samuel F SF Scheffer Ingrid E IE de Falco Fabrizio A FA Oliver Peter L PL Striano Pasquale P Zara Federico F Campeau Phillipe M PM Sisodiya S M SM

Neurology 20160608 1

<h4>Objective</h4>To evaluate the phenotypic spectrum associated with mutations in TBC1D24.<h4>Methods</h4>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).<h4>Results</h4>Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. Th ...[more]

PMID: 27281533

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Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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