2. Academic Validation
  3. Mutations in GNAL cause primary torsion dystonia

Mutations in GNAL cause primary torsion dystonia

  • Nat Genet. 2013 Jan;45(1):88-92. doi: 10.1038/ng.2496.
Tania Fuchs 1,  Rachel Saunders-Pullman,  Ikuo Masuho,  Marta San Luciano,  Deborah Raymond,  Stewart Factor,  Anthony E Lang,  Tsao-Wei Liang,  Richard M Trosch,  Sierra White,  Edmond Ainehsazan,  Denis Hervé,  Nutan Sharma,  Michelle E Ehrlich,  Kirill A Martemyanov,  Susan B Bressman,  Laurie J Ozelius
Affiliations

Affiliation

  • 1 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.
PMID: 23222958 DOI: 10.1038/ng.2496
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.

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