title: Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy.
abstract: Early-onset epileptic encephalopathies (EOEEs) are a group of rare devastating epileptic syndromes of infancy characterized by severe drug-resistant seizures and electroencephalographic abnormalities. The current study aims to determine the genetic etiology of a familial form of EOEE fulfilling the diagnosis criteria for malignant migrating partial seizures of infancy (MMPSI). We identified two inherited novel mutations in TBC1D24 in two affected siblings. Mutations severely impaired TBC1D24 expression and function, which is critical for maturation of neuronal circuits. The screening of TBC1D24 in an additional set of eight MMPSI patients was negative. TBC1D24 loss of function has been associated to idiopathic infantile myoclonic epilepsy, as well as to drug-resistant early-onset epilepsy with intellectual disability. Here, we describe a familial form of MMPSI due to mutation in TBC1D24, revealing a devastating epileptic phenotype associated with TBC1D24 dysfunction.
authors.affiliation: Inserm, U910, Marseille, France. mathieu.milh@ap-hm.fr
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.forename: Antonio
authors.initials: A
authors.lastname: Falace
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villeneuve
authors.forename: Nicola
authors.initials: N
authors.lastname: Vanni
authors.forename: Pierre
authors.initials: P
authors.lastname: Cacciagli
authors.forename: Stefania
authors.initials: S
authors.lastname: Assereto
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
authors.forename: Anna
authors.initials: A
authors.lastname: Fassio
mesh_terms: D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D059472:Exome; D005260:Female; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008565:Membrane Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins; D010641:Phenotype; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C552551:TBC1D24 protein, human