title: Mutations in GNAL cause primary torsion dystonia.
abstract: Dystonia is a movement disorder characterized by repetitive twisting muscle contractions and postures. Its molecular pathophysiology is poorly understood, in part owing to limited knowledge of the genetic basis of the disorder. Only three genes for primary torsion dystonia (PTD), TOR1A (DYT1), THAP1 (DYT6) and CIZ1 (ref. 5), have been identified. Using exome sequencing in two families with PTD, we identified a new causative gene, GNAL, with a nonsense mutation encoding p.Ser293* resulting in a premature stop codon in one family and a missense mutation encoding p.Val137Met in the other. Screening of GNAL in 39 families with PTD identified 6 additional new mutations in this gene. Impaired function of several of the mutants was shown by bioluminescence resonance energy transfer (BRET) assays.
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Tania
authors.initials: T
authors.lastname: Fuchs
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.forename: Ikuo
authors.initials: I
authors.lastname: Masuho
authors.forename: Marta San
authors.initials: MS
authors.lastname: Luciano
authors.forename: Deborah
authors.initials: D
authors.lastname: Raymond
authors.forename: Stewart
authors.initials: S
authors.lastname: Factor
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Tsao-Wei
authors.initials: TW
authors.lastname: Liang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Trosch
authors.forename: Sierra
authors.initials: S
authors.lastname: White
authors.forename: Edmond
authors.initials: E
authors.lastname: Ainehsazan
authors.forename: Denis
authors.initials: D
authors.lastname: Hervé
authors.forename: Nutan
authors.initials: N
authors.lastname: Sharma
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Ehrlich
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressman
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D002648:Child; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005190:Family; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D023061:Gene Order; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D044385:GTP-Binding Protein alpha Subunits; C084618:olfactory G protein subunit alpha olf