Since then, several other mutations have been described and implicated ARX in a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects such as Xlinked lissencephaly with abnormal genitalia , to milder forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy . Although Arx is expressed in several structures including the brain, pancreas, developing testes, heart, skeletal muscle and liver , the most striking consequences of Arx loss of function concern the brain and testis in both mouse and human. In the developing and adult brain, Arx is strongly expressed in telencephalic structures, particularly in populations of GABAcontaining neurons . Recent studies of the effects of Arx loss of function revealed that this gene contributes to almost all fundamental processes of brain development: patterning, neuronal proliferation and migration, neuronal maturation and differentiation as well as axonal outgrowth . Arx encodes a transcription factor which belongs to one of the three largest classes of homeoproteins, the paired class. Genes from this family are characterised by a 60-amino acid homeodomain responsible for DNA-binding. In addition, they often contain other motifs that can contribute to DNA and/or cofactor binding specificity. For example, the highly conserved octapeptide domain 133407-82-6 located in the N-terminal part of Arx, as well as another C-terminal region including the fourth polyalanine tract, have transcriptional repressor activity while the aristalessrelated domain, located at the C-terminus, has transcriptional activator activity . A few co-factors of Arx have been identified: the Groucho/transducin-like enhancer of split family of co-repressors interacts with Arx octapeptide, whereas repression by the second domain occurs through the interaction with C-terminal binding proteins . In addition, Arx has four polyalanine tracts. The two ones located in the Nterminal part of Arx seem particularly important for the function of the protein as several expansions have been identified in patients. For this type of mutations, it has recently been suggested that the level of transcriptional repression activity may depend on the length of the alanine expansion .