Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the PARKIN gene are associated with early-onset (juvenile) Parkinson's disease. We analyzed the coding sequence of this gene (exons 1-12) in patients from a family with three affected siblings, born to first-degree consanguineous parents, with an onset before 23 years and foot dystonia as the initial clinical symptom. The three patients were alive without cognitive impairment at ages of 70, 69, and 65 years, showing a marked response to levodopa treatment. A 2 bp-deletion at exon 11 (1276-1277 del GA) was found. The three patients were homozygous for this frameshift mutation, which would introduce a Stop at codon 394. This is a new PARKIN-mutation that would produce a truncated protein, lacking exon 12 and most the 11th. This region includes the C-terminal ring-finger domain of parkin, essential for its function as a ubiquitin-protein ligase. Compared to patients from other families with truncating mutations, our patients had an earlier onset. In addition, the three patients had dystonia at onset. In conclusion, we described a new PARKIN truncating mutation associated with an early onset parkinsonism, and the presence of foot dystonia as the initial symptom.
 ...
PMID:Early-onset Parkinson's disease associated with a new parkin mutation in a Spanish family. 1168 52

Angelman syndrome is a severe neurodevelopmental disorder with cognitive impairment and neurological deficits. It results from a maternal deletion of human chromosome 15q11-13 containing two candidate genes E6-P ubiquitin-protein ligase (UBE3A) and GABA(A) receptor beta3 subunit (GABRB3), the latter of which has been also linked to autism. To clarify the potential role of GABA(A) beta3 subunit-containing inhibitory receptors in these disorders, we applied ligand autoradiography on brain sections from mice with inactivated GABRB3 or maternal UBE3A genes. Binding of GABA(A) receptor channel ([(35)S]t-butylbicyclophosphorothionate) and benzodiazepine ([(3)H]Ro 15-4513) site ligands was reduced in selected brain regions of the beta3-deficient mice as compared to controls, while the UBE3A-deficient mice failed to show reduced GABA(A) receptors. The results, suggesting two different pathophysiological mechanisms, are in agreement with positron emission tomography results from Angelman syndrome patients of the corresponding genetic backgrounds.
 ...
PMID:Mouse models of Angelman syndrome, a neurodevelopmental disorder, display different brain regional GABA(A) receptor alterations. 1267 42