The aristaless (Arx) gene: one gene for many "interneuronopathies"
Martino Ruggieri1, Piero Pavone2, Giovanni Scapagnini3, Loriana Romeo1, Ilaria Lombardo4, Giovanni Li Volti 5,6, Giovanni Corsello7, Lorenzo Pavone4
1
Institute of Neurological Science (ISN), National Research Council (CNR), Catania, Italy, 2 Unit of Pediatrics, University Hospital "Vittorio Emanuele", Catania, Italy,3 Department of Health Sciences, University of Molise, Campobasso, Italy,4 Unit of Clinical Pediatrics, Department of Pediatrics, University of Catania, Italy,5 Department of Biological Chemistry, Faculty of Pharmacy, University of Catania, Italy,6 IRCCS Associazione Oasi Maria S.S.- Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Italy,7 Maternal-Infantile Department, University of Palermo, Italy
TABLE OF CONTENTS
- 1. Abstract
- 2. The "arista" and the aristaless (al)-related family of genes
- 3. The ARX(aristaless-related) genes and their homeodomain protein products
- 4. Phenotypic heterogeneity associated with ARX abnormalities
- 4.1. Ohtahara Syndrome
4.1.1. Clinical features of Ohtahara syndrome 4.1.2. Interictal EEG findings
- 4.1.3. Brain imaging 4.2. Clinical features of infantile spasms and West Syndrome
- 4.3. Partington (X-linked) mental retardation syndrome
- 4.4. Non-specific X-linked mental retardation
- 4.5. X-linked Lissencephaly with abnromal genitalia
- 4.6. Proud Syndrome
- 4.7. X-linked mental retardation and epilepsy with combination of infantile spasms and non-ictal complex dyskinetic
- 4.8. Parietal foramina-2 syndrome
5. Additional effects of ARX mutations - ARX vs. Stxbp1 gene: mutual transition/evolution of Ohtahara syndrome into other early infantile epileptic encephalopathies (EIEE)
5.1. Role of ARX gene
5.2. Role of Stxbp1 gene
6. Concluding remarks
7. Aknowledgements
8. References
1. ABSTRACT
The ARX (Aristaless-related (X-linked) homeobox) gene is not only present in arthropods and their ancestors, but also in vertebrates including humans (ARX orthologs). The gene is composed of 5 coding exons and it is expressed predominantly in foetal and adult brain and skeletal muscle. In this review we report on our experience and review the existing literature on the genotype and phenotype heterogeneity associated with ARX abnormalities in humans ranging from severe neuronal migration defects (e.g., lissencephaly), to mild forms of X-linked mental retardation without apparent brain abnormalities. The ARX-related disorders are reviewed focusing on their clinical features and on the role of the ARX gene. It has yet to be established whether the molecular defect alone could cause a given cerebral abnormality and/or malformation or an additional or related molecular or environmental event could contribute to a given phenotype in molecularly
