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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the human ARX gene show unusually heterogeneous clinical presentations, including syndromic and nonsyndromic mental retardation, myoclonic epilepsy with spasticity, and lissencephaly with abnormal genitalia, that are believed to arise from an impairment of the embryonic mechanisms building the anterior central nervous system structures. Here, we show that the murine ortholog Arx has a highly dynamic expression pattern during both early shaping of the forebrain vesicle and later major events of neural migrations and cell-type specification. Early on, the Arx gene is specifically activated in anterior forebrain anlage. Afterward, Arx expression is confined to the telencephalic vesicles and is enhanced during differentiation of the subpallial structures of the ganglionic eminences, overlapping with Dlx2, Dlx5, and Gad1 transcriptional domains. Tangentially migrating neurons reaching the cortical plate are also Arx-positive at all embryonic stages analyzed. RNA-protein colabeling staining shows that Arx expression is maintained in the mature cortical interneurons, suggesting its involvement in the different functions of the gamma-aminobutyric acid (GABA)ergic neurons settled into the adult cerebral cortex. Finally, Arx expression is detected in the anterior subventricular layer of the adult brain, where neural stem cells have been shown to be located. Of interest, Arx expression is highly up-regulated during in vitro differentiation of pure neural stem cell cultures retrieved from adult brain. All together, these findings suggest Arx as a gene involved in the commitment of proliferating neuroblasts into a GABAergic neuronal fate. In conclusion, our mouse Arx expression data provide important further insights into the puzzling complexity of the human ARX mutation pleiotropy.
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PMID:Mouse orthologue of ARX, a gene mutated in several X-linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons. 1537 19

We screened 165 mentally retarded patients for ARX gene 428-451 base pair (bp) duplication. Eighteen individuals from five families were found to carry the duplication, and all had intellectual impairment. Twelve presented with focal hand dystonia, while six patients had EEG abnormalities including seizures. Other symptoms included speech difficulties (4/18), testis enlargement (4/18), lower limb spasticity or foot dystonia (4/18), and facial telangiectasia (3/18). These features confirm the pleiotropic effect of the duplication.
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PMID:Genotype-phenotype associations for ARX gene duplication in X-linked mental retardation. 1708 67

ARX (Aristaless-related homeobox gene) is located at Xp22. It contains 5 exons and encodes a 562-amino acid protein. The protein contains 4 polyalanine tracts, 3 of which are encoded in exon 2 and 1 in exon 4. Mutations in the ARX gene have been found in X-linked infantile spasms syndrome, Partington syndrome (mental retardation with dystonic movements of the hands), X-linked lissencephaly with abnormal genitalia, X-linked myoclonus epilepsy with spasticity and intellectual disability, and in nonsyndromic X-linked mental retardation. The most common mutation in ARX (seen in X-linked infantile spasms syndrome, Partington syndrome, and X-linked mental retardation) is a 24-bp duplication in exon 2 resulting in expansion of a polyalanine tract. Truncating mutations (deletions, frameshift, non-sense) have been found in X-linked lissencephaly with abnormal genitalia, as well as homeodomain missense mutations in X-linked myoclonus epilepsy with spasticity and intellectual disability. The authors report a novel 24-bp in-frame deletion within exon 2 of the ARX gene in a male child with X-linked mental retardation and review the spectrum of ARX mutations. This mutation results in a contraction of the second polyalanine repeat.
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PMID:A novel mutation of the ARX gene in a male with nonsyndromic mental retardation. 1764 Dec 62

Mental retardation is a serious social problem. It affects 2-3% of the population. It is estimated that mutations in the ARX gene can be found in 1 in 12,000 live male births. This is the second most common cause of X-linked mental retardation after fragile X syndrome. The ARX gene belongs to transcription factors involved in differentiation of specific neuronal cells in the central nervous system. The most common mutation in the ARX gene is c. 428_451dup24, duplication of 24 bp in exon 2 of the gene, causing elongation of the second alanine tract (polyA12_II). Described disorders caused by mutations in the ARX gene include: hydrocephaly with abnormal genitalia (HYD-AG), lissencephaly with abnormal genitalia (XLAG), agenesis of corpus callosum with abnormal genitalia (ACC-AG), Partington syndrome (PRTS), X-linked infantile spasms (ISSX), myoclonic epilepsy with spasticity and mental retardation (XMESID), and nonspecific mental retardation (NS-XLMR).
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PMID:[ARX--one gene--many phenotypes]. 1897 39