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Novel Compound Heterozygous Mutations in TBC 1 D 24 Cause Familial Malignant Migrating Partial Seizures of Infancy
Author(s) -
Milh Mathieu,
Falace Antonio,
Villeneuve Nathalie,
Vanni Nicola,
Cacciagli Pierre,
Assereto Stefania,
Nabbout Rima,
Benfenati Fabio,
Zara Federico,
Chabrol Brigitte,
Villard Laurent,
Fassio Anna
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22318
Subject(s) - epilepsy , mutation , etiology , biology , neuroscience , phenotype , intellectual disability , partial seizures , genetics , medicine , pathology , gene
Early‐onset epileptic encephalopathies ( EOEE s) 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 TBC 1 D 24 in two affected siblings. Mutations severely impaired TBC 1 D 24 expression and function, which is critical for maturation of neuronal circuits. The screening of TBC 1 D 24 in an additional set of eight MMPSI patients was negative. TBC 1 D 24 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 TBC 1 D 24 , revealing a devastating epileptic phenotype associated with TBC 1 D 24 dysfunction.