title: A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia.
abstract: The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi.
authors.affiliation: Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Corbett
authors.forename: Michael
authors.initials: M
authors.lastname: Schwake
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Meng
authors.initials: M
authors.lastname: Lin
authors.forename: Luke C
authors.initials: LC
authors.lastname: Gandolfo
authors.forename: Danya F
authors.initials: DF
authors.lastname: Vears
authors.forename: John D
authors.initials: JD
authors.lastname: O'Sullivan
authors.forename: Thomas
authors.initials: T
authors.lastname: Robertson
authors.forename: Marta A
authors.initials: MA
authors.lastname: Bayly
authors.forename: Alison E
authors.initials: AE
authors.lastname: Gardner
authors.forename: Annemarie M
authors.initials: AM
authors.lastname: Vlaar
authors.forename: G Christoph
authors.initials: GC
authors.lastname: Korenke
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.forename: Irenaeus F
authors.initials: IF
authors.lastname: de Coo
authors.forename: Judith M A
authors.initials: JM
authors.lastname: Verhagen
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D006056:Golgi Apparatus / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D050766:Qb-SNARE Proteins / Q000235:genetics*; D050600:SNARE Proteins / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000473:pathology
chemical_list: C491344:GOSR2 protein, human; D005819:Genetic Markers; D050766:Qb-SNARE Proteins; D050600:SNARE Proteins