Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Childhood absence epilepsy (CAE), one of the most common epilepsies in children, is genetically and phenotypically heterogeneous. One of the genes responsible for human CAE associated with tonic-clonic seizures has been mapped to chromosome band 8q24 by genetic linkage analysis and is termed ECA1. Recently, we isolated and mapped the JRK/JH8 gene, a human homologue of the mouse epilepsy gene, jerky, on 8q24. The epilepsy phenotype of the mice with inactivated jerky gene as well as its chromosomal localization proposed JRK/JH8 as a prominent candidate for the CAE gene. To confirm whether the JRK/JH8 gene is responsible for ECA1, we performed mutational analyses in the coding region of JRK/JH8 in two CAE families mapped on 8q24, using heteroduplex and direct sequencing methods. We identified seven nucleotide changes, two of which lead to amino acid substitutions. However, these changes did not co-segregate with the disease phenotype. In addition, we redefined the location of JRK/JH8 to be more than 4 Mb distant from D8S502 and ECA1. Thus, negative results of mutation analyses and detailed physical mapping exclude JRK/JH8 as the ECA1 gene.
 ...
PMID:Exclusion of the JRK/JH8 gene as a candidate for human childhood absence epilepsy mapped on 8q24. 1051 Sep 81

Disruption of the function of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy (IGE). A human homologue, JRK/JH8, has been cloned, which maps to 8q24, a chromosomal region associated with several forms of IGE. JRK/JH8 is, therefore, a candidate locus for at least some forms of IGE. We report corrected cDNA sequences and extended open reading frames for the mouse jerky and human JRK/JH8 genes, which add 48 amino acids to the N-terminus of the Jerky protein and which extends the region of homology with the N-terminal DNA-binding domain of the centromere-binding protein, CENP-B. Systematic sequencing of the coding region of the extended JRK/JH8 gene identified single nucleotide polymorphisms that define three haplotypes, which were used for association studies in patients with idiopathic generalized epilepsy. We report one subject with childhood absence epilepsy (CAE) that evolved to juvenile myoclonic epilepsy (JME) that has a unique de novo mutation that results in a non-conservative amino acid change at a potential protein glycosylation site. Familial analysis supports a causal role for this mutation in the disease.
 ...
PMID:Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and description of a rare mutation in a case of CAE evolving to JME. 1146 17

The mouse jerky gene and its human orthologue, JRK/JH8, encode a putative DNA-binding protein with homology to the CENP-B (centromere-binding protein B). Disruption of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy. In addition (and similar to a cenp-b null mouse) jerky null mice exhibit postnatal weight loss and reduced fertility. Using fluorescence confocal microscopy, the cellular localization of a JRK-GFP fusion (where GFP stands for green fluorescent protein) was investigated in HeLa cells. JRK-GFP has a dynamic expression pattern in the interphase nucleus, localizing in a small number of punctate nuclear foci and in the nucleolus. The JRK-GFP foci number changes during the cell cycle, but a distinct pattern of three JRK-GFP foci is observed at G(2). The endogenous protein behaves in a similar manner to the GFP-fusion protein. JRK-GFP was found to co-localize with CREST antigens (which recognize the centromere-binding proteins, CENP-A, -B and -C) through S and G(2) phases of interphase and co-localized completely with a subset of PML nuclear bodies at G(2). We speculate that JRK protein associates with a specific chromosomal centromeric locus in G(2), where it associates fully with PML bodies. Research is underway to identify this locus.
 ...
PMID:Complex regulation and nuclear localization of JRK protein. 1550 25