ARX gene as a genetic marker for catastrophic neurological disorders and related conditions

摘要

ARX, the aristaless-related homeobox gene, is involved in the development of cerebral GABAergic interneurons. Mutations of ARX cause a wide variety of X-linked neurological disorders, designated as interneuronopathies, with a strong correlation between genotype and phenotype. Null mutations in ARX cause brain malformation group, such as X-linked lissencephaly with abnormal genitalia (XLAG), hydranen-cephaly, and agenesis of the corpus callosum. Patients with XLAG have intractable seizures from the first day of life, and neuropathological studies demonstrate loss of neocortical pyramidal neurons serving as inhibitory transmission. Expansion mutations of the first or second polyalanine tract result in a non-malformation group, such as mental retardation, dystonia, West syndrome, and Ohtahara syndrome. Expansion size is correlated with the onset or severity of neurological symptoms, suggesting a molecular mechanism of age-dependent epileptic encephalopathies.