Mutations in the GABAA receptor β3 subunit gene (GABRB3) are implicated in childhood absence epilepsy, according to research published online May 29 in the American Journal of Human Genetics.
THURSDAY, June 5 (HealthDay News) -- Mutations in the GABAA receptor β3 subunit gene (GABRB3) are implicated in childhood absence epilepsy, according to research published online May 29 in the American Journal of Human Genetics.
Miyabi Tanaka, of the University of California Los Angeles, and colleagues analyzed the DNA of 48 patients with childhood absence epilepsy and their family members. Families were from Mexico, Honduras and El Salvador.
The researchers found GABRB3 mutations in 8 percent of families: a heterozygous missense mutation (P11S) in two-generation family; a heterozygous missense mutation (S15F) in another patient; and a heterozygous missense mutation (G32R) in two patients in a family. These mutations were absent in 630 controls. Two of the mutations -- P11S and S15F -- are found in the alternative signal peptide exon 1a of the GABRB3 protein, which is found in smaller amounts in adult brains compared to fetal brains.
"The mutations in GABRB3 described here are associated with a gain in glycosylation of the β3 subunit protein. Glycosylation of the β3 subunit protein is known to change its maturation, and alter overall GABAR trafficking to the cell surface from endoplasmic reticulum. We suggest that the resulting hyperglycosylation and reduced current densities of the mutated β3 subunit protein leads to absence seizures. Our results also allow us to hypothesize that mutated exon 1a lead to an abnormal isoform 2 precursor of GABRB3 polipeptide during development. This in turn, may explain the decrease/disappearance of absence seizures in adolescents and adults," the authors write.
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