Thevenon J.,University of Burgundy |
Milh M.,Service de Neurologie Pediatrique |
Milh M.,Aix - Marseille University |
Feillet F.,University of Lorraine |
And 28 more authors.
American Journal of Human Genetics | Year: 2014
Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy. © 2014 The American Society of Human Genetics.
Bonnet C.,French Institute of Health and Medical Research |
Roubertie A.,Departement de Neurologie Pediatrique |
Roubertie A.,Commission Mouvements Anormaux de la Societe Francaise de Neurologie Pediatrique |
Doummar D.,Commission Mouvements Anormaux de la Societe Francaise de Neurologie Pediatrique |
And 7 more authors.
Movement Disorders | Year: 2010
Developmental and benign movement disorders are a group of movement disorders with onset in the neonatal period, infancy, or childhood. They are characterized by the absence of associated neurological manifestations and by their favorable outcome, although developmental abnormalities can be occasionally observed. Knowledge of the clinical, neurophysiological, and pathogenetic aspects of these disorders is poor. Based on a comprehensive review of the literature and our practical experience, this article summarizes current knowledge in this area. We pay special attention to the recognition and management of these movement disorders in children. © 2010 Movement Disorder Society.