Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia.

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Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia. / Vemula, Satya R; Puschmann, Andreas; Xiao, Jianfeng; Rudzinska, Monika; Frei, Karen P; Truong, Daniel D; Wszolek, Zbigniew K; LeDoux, Mark S.

I: Human Molecular Genetics, Vol. 22, Nr. 12, 2013, s. 2510-2519.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Vemula, SR, Puschmann, A, Xiao, J, Rudzinska, M, Frei, KP, Truong, DD, Wszolek, ZK & LeDoux, MS 2013, 'Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia.', Human Molecular Genetics, vol. 22, nr. 12, s. 2510-2519. https://doi.org/10.1093/hmg/ddt102

APA

Vemula, S. R., Puschmann, A., Xiao, J., Rudzinska, M., Frei, K. P., Truong, D. D., ... LeDoux, M. S. (2013). Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia. Human Molecular Genetics, 22(12), 2510-2519. https://doi.org/10.1093/hmg/ddt102

CBE

Vemula SR, Puschmann A, Xiao J, Rudzinska M, Frei KP, Truong DD, Wszolek ZK, LeDoux MS. 2013. Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia. Human Molecular Genetics. 22(12):2510-2519. https://doi.org/10.1093/hmg/ddt102

MLA

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Author

Vemula, Satya R ; Puschmann, Andreas ; Xiao, Jianfeng ; Rudzinska, Monika ; Frei, Karen P ; Truong, Daniel D ; Wszolek, Zbigniew K ; LeDoux, Mark S. / Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia. I: Human Molecular Genetics. 2013 ; Vol. 22, Nr. 12. s. 2510-2519.

RIS

TY - JOUR

T1 - Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia.

AU - Vemula, Satya R

AU - Puschmann, Andreas

AU - Xiao, Jianfeng

AU - Rudzinska, Monika

AU - Frei, Karen P

AU - Truong, Daniel D

AU - Wszolek, Zbigniew K

AU - LeDoux, Mark S

PY - 2013

Y1 - 2013

N2 - The vast majority of patients with primary dystonia are adults with focal or segmental distribution of involuntary movements. Although approximately 10% of probands have at least one first- or second-degree relative with 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 3 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 [Gα(olf)]. Gα(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 up-regulation of genes involved in cell cycle control and development. Consistent with known sites of network pathology in dystonia, immunohistochemical studies indicated that Gα(olf) is highly expressed in the striatum and cerebellar Purkinje cells, and co-localized with corticotropin-releasing hormone receptors in the latter.

AB - The vast majority of patients with primary dystonia are adults with focal or segmental distribution of involuntary movements. Although approximately 10% of probands have at least one first- or second-degree relative with 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 3 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 [Gα(olf)]. Gα(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 up-regulation of genes involved in cell cycle control and development. Consistent with known sites of network pathology in dystonia, immunohistochemical studies indicated that Gα(olf) is highly expressed in the striatum and cerebellar Purkinje cells, and co-localized with corticotropin-releasing hormone receptors in the latter.

KW - dystonia

KW - genetics

KW - neurogenetics

KW - movement disorders

KW - GNAL

KW - olfaction

KW - Purkinje cell

U2 - 10.1093/hmg/ddt102

DO - 10.1093/hmg/ddt102

M3 - Article

VL - 22

SP - 2510

EP - 2519

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 12

ER -