Aristaless-related homeobox gene, the gene responsible for West syndrome and related disorders, is a Groucho/transducin-like enhancer of split dependent transcriptional repressor.

Aristaless-related homeobox gene (ARX) is an important paired-type homeobox gene involved in the development of human brain. The ARX gene mutations are a significant contributor to various forms of X-chromosome-linked mental retardation with and without additional features including epilepsy, lissencephaly with abnormal genitalia, hand dystonia or autism. Here we demonstrate that the human ARX protein is a potent transcriptional repressor, which binds to Groucho/transducin-like enhancer of split (TLE) co-factor proteins and the TLE1 in particular through its octapeptide (Engrailed homology repressor domain (eh-1) homology) domain. We show that the transcription repression activity of ARX is modulated by two strong repression domains, one located within the octapeptide domain and the second in the region of the polyalanine tract 4, and one activator domain, the aristaless domain. Importantly, we show that the transcription repression activity of ARX is affected by various naturally occurring mutations. The introduction of the c.98T>C (p.L33P) mutation results in the lack of binding to TLE1 protein and relaxed transcription repression. The introduction of the two most frequent ARX polyalanine tract expansion mutations increases the repression activity in a manner dependent on the number of extra alanines. Interestingly, deletions of alanine residues within polyalanine tracts 1 and 2 show low or no effect. In summary we demonstrate that the ARX protein is a strong transcription repressor, we identify novel ARX interacting proteins (TLE) and offer an explanation of a molecular pathogenesis of some ARX mutations, including the most frequent ARX mutations, the polyalanine tract expansion mutations, c.304ins(GCG)7 and c.428_451dup.

Premarket evaluation of IDS RapID SS/u system for identification of urine isolates.

A total of 170 fresh clinical urine isolates were tested with a premarket configuration of the RapID SS/u system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.), a qualitative micromethod for the identification of selected organisms commonly isolated from urine specimens. Results were compared with those obtained with conventional methods of identifying gram-positive isolates and with the AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.), utilizing Gram-Negative Identification cards for the identification of gram-negative rods. Organisms representing 12 taxa were included in the study. Of the 170 isolates, 163 (95.9%) were correctly identified. A total of 144 strains (84.7%) were correctly identified without additional testing, whereas 19 isolates (11.2%) required further testing. Seven isolates (4.1%) were incorrectly identified. The SS/u system required minimal hands-on time inoculate and interpret reactions. Discrepancies most often occurred with regard to misinterpretation of Escherichia coli and Enterobacter sp. as Citrobacter sp. The IDS RapID SS/u system may indeed prove valuable for the rapid manual identification of urine isolates.