title: Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q.
abstract: Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. We performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region.
authors.affiliation: Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284.
authors.forename: S G
authors.initials: SG
authors.lastname: Ryan
authors.forename: M J
authors.initials: MJ
authors.lastname: Dixon
authors.forename: M A
authors.initials: MA
authors.lastname: Nigro
authors.forename: K A
authors.initials: KA
authors.lastname: Kelts
authors.forename: O N
authors.initials: ON
authors.lastname: Markand
authors.forename: J C
authors.initials: JC
authors.lastname: Terry
authors.forename: R
authors.initials: R
authors.lastname: Shiang
authors.forename: J J
authors.initials: JJ
authors.lastname: Wasmuth
authors.forename: P
authors.initials: P
authors.lastname: O'Connell
mesh_terms: D001483:Base Sequence; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D002998:Clonazepam / Q000627:therapeutic use; D004277:DNA, Single-Stranded; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011963:Receptors, GABA-A / Q000187:drug effects; D016750:Stiff-Person Syndrome / Q000188:drug therapy / Q000235:genetics*
chemical_list: D004277:DNA, Single-Stranded; D011963:Receptors, GABA-A; D002998:Clonazepam