Objective: To identify human genes encoding neuronal voltage-gated calcium channel γ subunits corresponding to the γ subunit recently described in mice with hereditary epilepsy, confirm their expression in adult brain, and determine whether a γ subunit resides in human chromosomal regions with marker genes linked to convulsions. Material and Methods: Human homologues of a recently described mouse γ subunit were sought by a computerized search of National Center for Biotechnology Information databases. Sequences of interest were mapped electronically to specific chromosomal regions. The proximity of these chromosomal regions to markers linked to convulsive disorders was determined by a MEDLINE search. Predicted γ subunit sequences were amplified by polymerase chain reaction from a human adult brain complementary DNA (cDNA) library and were subcloned, and full- length sequences were determined or confirmed. Secondary structure and transmembrane regions were predicted by using the TMpredict program. Results: Two putative isoforms (human γ-2 and γ-3 calcium channel subunits) were identified, cloned, and sequenced. They mapped to chromosomes 22 and 16, respectively. A marker very close to the γ-3 gene gives maximal lod scores for an autosomal dominant syndrome of familial infantile convulsions and paroxysmal choreoathetosis. Conclusion: Genomic DNA sequence data already existed in GenBank (partial for γ-2 and complete for γ-3) for the two putative neuronal calcium channel γ subunits that we identified. By cloning both of these molecules from a cerebellar cDNA library, we demonstrated for the first time their expression in human brain. The γ-3 gene is adjacent to a marker for a convulsive disorder. The convulsive phenotype of γ channelopathies occurring in mice makes the human γ subunit genes attractive candidate genes for hereditary convulsive disorders.
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