Peripheral markers of the gamma-aminobutyric acid (GABA)ergic system in Angelman's syndrome.
It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three gamma-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in the deleted region, a possible modification of peripheral markers of the GABAergic system was investigated in 12 subjects with Angelman's syndrome and 20 age-matched subjects (8 with idiopathic epilepsy and 12 not affected by neurologic diseases). The results confirmed a more severe clinical picture, and epilepsy syndrome in particular, in Angelman's syndrome patients with deletions versus patients without deletions. In contrast, biochemical study (based on dosage of plasma levels of GABA and diazepam binding inhibitor, an endogenous ligand of GABAA and peripheral benzodiazepine receptors, showed contradictory results: patients with Angelman's syndrome showed significantly higher levels of GABA and diazepam binding inhibitor than patients without neurologic impairment but significantly lower levels than epileptic controls.
Borgatti
Renato
R
Scientific Institute Eugenio Medea, Bosisio Parini, Lecco, Italy. borgatti@bp.lnf.it
Piccinelli
Paulo
P
Passoni
Davide
D
Romeo
Antonino
A
Viri
Maurizio
M
Musumeci
Sebastiano A
SA
Elia
Maurizio
M
Cogliati
Tiziana
T
Valseriati
Daniela
D
Grasso
Rita
R
Raggi
Maria E
ME
Ferrarese
Carlo
C
D000293:Adolescent; D000328:Adult; D017204:Angelman Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D026261:Diazepam Binding Inhibitor / Q000097:blood*; D004828:Epilepsies, Partial / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D004829:Epilepsy, Generalized / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D011963:Receptors, GABA-A / Q000097:blood* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000097:blood*
D026261:Diazepam Binding Inhibitor; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid