Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts
Neonatal epileptic encephalopathies with suppression bursts (SBs) are very severe and relatively rare diseases characterized by neonatal onset of seizures, interictal electroencephalogram (EEG) with SB pattern and very poor neurological outcome or death. Their etiology remains elusive but they are occasionally caused by metabolic diseases or malformations. Studying an Arab Muslim Israeli consanguineous family, with four affected children presenting a severe neonatal epileptic encephalopathy, we have previously identified a mutation in the SLC25A22 gene encoding a mitochondrial glutamate transporter. In this report, we describe a novel SLC25A22 mutation in an unrelated patient born from first cousin Algerian parents and presenting severe epileptic encephalopathy characterized by an EEG with SB, hypotonia, microcephaly and abnormal electroretinogram. We showed that this patient carried a homozygous p.G236W SLC25A22 mutation which alters a highly conserved amino acid and completely abolishes the glutamate carrier's activity in vitro. Comparison of the clinical features of patients from both families suggests that SLC25A22 mutations are responsible for a novel clinically recognizable epileptic encephalopathy with SB.
Document Type: Research Article
Affiliations: 1: Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari, Bari, Italy 2: Service de radiologie pédiatrique, U797, Hôpital Necker-Enfants Malades, AP-HP, Paris, France 3: Department of Human Genetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel 4: Unité de Physiologie et d’exploration fonctionnelle (INSERM U663), Groupe Hospitalier Necker-Enfants Malades, APHP, Paris, France 5: Neurologie pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Epilepsie et plasticité cérébrale (INSERM U663), Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France
Publication date: August 1, 2009