Anti-GABRA5 polyclonal antibody

Angelman (AS), Prader-Willi (PWS) and Inv Dup(15) (IDS) syndromes are different disorders linked to alterations of chromosome 15. We considered 34 patients: 21 with AS, 7 with PWS and 6 with IDS, in which the clinical and neuropsychological features do not differ from the literature data. Since genes for three GABA-A receptor subunits (GABRB3, GABRA5 and GABRG3) map in this chromosome region, the GABAergic system can be involved in some neurological manifestations of these syndromes. For this reason, we evaluated the plasma levels of Diazepam Binding Inhibitor (DBI), a putative modulator of GABAergic system; cortisol, ACTH, thyroid hormones and gonadotropines to analize the hypotalamus-hypophysis axis; and the urinary excretion of serotonin and catecolamine metabolites as peripheral markers of the serotoninergic and noradrenergic systems. We also excluded an hypotalamo-hypophysis axis alteration as origin of the clinical manifestations. On the other hand our patients showed a significant reduction (p<0,05) in the urinary excretion of serotonin and catecolamines catabolites in PWS subjects compared with AS subjects; in particulary we observed a reduction of about 50% in the urinary escretion of the principal serotonin metabolite (5-hydroxi-indolacetic acid) in the PWS patients compared with a control group. This result can be correlated to the clinical relevance of sleep disorders and behavioural disturbances typical of these patients. Finally the DBI showed significantly higher levels in the AS and PWS patients when compared either with control subjects (p<0,001) and IDS patients (p<0,05), while it do not show any difference between AS and PWS subjects.

Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by onset of typical absence seizures; in otherwise normal children of school age. A genetic component to aetiology is wen established but the mechanism of inheritance and the genes involved are unknown. Available evidence suggests that mutations in genes encoding GABA receptors or brain expressed voltage-dependent calcium channels (VDCCs) may underlie CAE. The aim of this work was to test this hypothesis by linkage analysis using microsatellite loci spanning theses genes in 33 nuclear families each with two or more individuals with CAE. Seventeen VDCC subunit genes, ten GABA(A)R subunit genes, two GABA(B) receptor genes and the ECA1 locus on 8q24 were investigated using 35 microsatellite loci. Assuming locus homogeneity, all loci gave statistically significant negative LOD scores, excluding these genes as major loci in the majority of these families. Positive HLOD scores assuming locus heterogeneity were observed for CACNG3 on chromosome 16p12-p13.1 and the GABRA5, GABRB3, G4BRG3 cluster on chromosome 15q11-q13. Association studies are required to determine whether these loci are the site of susceptibility alleles in a subset of patients with CAE. (C) 2002 Elsevier Science B.V. All rights reserved.