ISSN:
1364-6753
Schlagwort(e):
Key words GABABR1 gene
;
Genomic organization
;
Idiopathic generalized epilepsy
;
Juvenile myoclonic epilepsy
;
Mapping
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
ABSTRACT Neurophysiological and pharmacological studies suggest a major role of the GABAB receptor in the epileptogenesis of absence seizures. The gene encoding the human GABABR1 receptor (GABA B R1) has recently been mapped to human chromosome 6p21.3 by in situ hybridization, a region that harbors a susceptibility locus (EJM1) for idiopathic generalized epilepsy (IGE). We investigated the hypothesis that the GABA B R1 gene (GABBR1) represents a candidate gene for EJM1 by: (1) defining the precise localization approximately 130 kilobases telomeric to the HLA-F locus, (2) by characterizing its genomic organization, and (3) by mutation screening of the entire coding region of GABBR1 in 18 German patients with juvenile myoclonic epilepsy (JME) who were derived from families with evidence for linkage to chromosome 6p21.3 (cumulative lod score Z=3.17 at HLA-DQ). The GABAB receptor gene consists of 22 translated exons. The two alternative transcripts, GABA B R1a and GABA B R1b, are derived from the same locus but they differ in their alternative 5′-exons. Mutation analyses in JME revealed several DNA sequence polymorphisms, two of which result in amino acid changes occurring in all IGE-affected members of two families. However, clinically unaffected relatives did carry the same variations, excluding these amino acid substitutions as the cause for IGE in these families.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s100480050051
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