Role of Gα(olf) in familial and sporadic adult-onset primary dystonia

Satya R. Vemula, Andreas Puschmann, Jianfeng Xiao, Yu Zhao, Monika Rudzińska, Karen P. Frei, Daniel D. Truong, Zbigniew K. Wszolek, Mark S. LeDoux

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


The vast majority of patients with primary dystonia are adults with focal or segmental distribution of involuntary movements. although ̃10% of probands have at least one first- or second-degree relative to dystonia, large families suited for linkage analysis are exceptional. after excluding mutations in known primary dystonia genes (tor1a, thap1 and ciz1), whole-exome sequencing identified a gnal missense mutation (c.682g>t, p.v228f) in an african-american pedigree with clinical phenotypes that include cervical, laryngeal and hand-forearm dystonia. screening of 760 subjects with familial and sporadic primary dystonia identified three caucasian pedigrees with gnal mutations [c.591dupa (p.r198tfs-13); c.733c>t (p.r245-); and c.3g>a (p.m1?)]. these mutations show incomplete penetrance. our findings corroborate those of a recent study which used whole-exome sequencing to identify missense and nonsense gnal mutations in caucasian pedigrees of mixed european ancestry with mainly adult-onset cervical and segmental dystonia. gnal encodes guanine nucleotide-binding protein g(olf), subunit alpha [ga(olf)]. ga(olf) plays a role in olfaction, coupling d1 and a2a receptors to adenylyl cyclase, and histone h3 phosphorylation. african-american subjects harboring the p.v228f mutation exhibited microsmia. lymphoblastoid cell lines from subjects with the p.v228f mutation showed upregulation of genes involved in cell cycle control and development. consistent with known sites of network pathology in dystonia, immunohistochemical studies indicated that ga(olf) is highly expressed in the striatum and cerebellar purkinje cells, and co-localized with corticotropin-releasing hormone receptors in the latter.

Original languageEnglish (US)
Pages (from-to)2510-2519
Number of pages10
JournalHuman molecular genetics
Issue number12
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Role of Gα(olf) in familial and sporadic adult-onset primary dystonia'. Together they form a unique fingerprint.

Cite this