[Topics of brain malformation and epilepsy--age-dependent epileptic encephalopathies and interneuronopathies].
The ARX gene is involved in the development of GABAergic interneurons in the forebrain. Loss-of-function mutations, such as nonsense or frameshifts mutation, of ARX cause a group of brain malformations, such as hydranencephaly, lissencephaly, and agenesis of the corpus callosum, while expansion mutations of the polyalanine tracts of ARX, supposed to be gain-of-function mutations, result in a non-malformation group, such as non-syndromic mental retardation, mental retardation with dystonia, West syndrome, and Ohtahara syndrome. A variety of phenotypes caused by pleiotropic mutations of the ARX gene are considered to share a common pathological mechanism connected with the structural and functional disturbance of interneurons, designated as 'interneuronopathies'. We identified the second gene responsible for Ohtahara syndrome, STXBP1, which is essential for synaptic vesicle release. Molecular studies of the diseases will reveal the relationships between the structure and function of the brain. It is indispensable to clarify the etiology of hereditary diseases and identify new approaches to treatment.
Kato
Mitsubiro
M
Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata. mkato@med.id.yamagata-u.ac.jp
D001921:Brain / Q000002:abnormalities*; D004827:Epilepsy / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007395:Interneurons / Q000473:pathology* / Q000502:physiology; D051938:Munc18 Proteins / Q000235:genetics; D009154:Mutation; D010455:Peptides / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
C469264:ARX protein, human; D018398:Homeodomain Proteins; D051938:Munc18 Proteins; D010455:Peptides; C497937:STXBP1 protein, human; D014157:Transcription Factors; C019529:polyalanine; D005680:gamma-Aminobutyric Acid