Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability

doi:10.1212/NXG.0000000000000106

. 2016 Sep 13;2(5):e106.

doi: 10.1212/NXG.0000000000000106. eCollection 2016 Oct.

Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability

Sofia Steinrücke¹, Katja Lohmann¹, Aloysius Domingo¹, Arndt Rolfs¹, Tobias Bäumer¹, Juliane Spiegler¹, Corinna Hartmann¹, Alexander Münchau¹

Affiliations

Affiliation

¹ Institute of Neurogenetics (S.S., K.L., A.D., T.B., C.H., A.M.), University of Lübeck; Albrecht-Kossel-Institute for Neuroregeneration (A.R.), University of Rostock; Centogene AG (A.R.), Rostock; and Department of Pediatrics (J.S.), University Medical Center Schleswig-Holstein, Campus Lübeck, Germany.

PMID: 27668284
PMCID: PMC5022844
DOI: 10.1212/NXG.0000000000000106

Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability

Sofia Steinrücke et al. Neurol Genet. 2016.

. 2016 Sep 13;2(5):e106.

doi: 10.1212/NXG.0000000000000106. eCollection 2016 Oct.

Authors

Sofia Steinrücke¹, Katja Lohmann¹, Aloysius Domingo¹, Arndt Rolfs¹, Tobias Bäumer¹, Juliane Spiegler¹, Corinna Hartmann¹, Alexander Münchau¹

Affiliation

¹ Institute of Neurogenetics (S.S., K.L., A.D., T.B., C.H., A.M.), University of Lübeck; Albrecht-Kossel-Institute for Neuroregeneration (A.R.), University of Rostock; Centogene AG (A.R.), Rostock; and Department of Pediatrics (J.S.), University Medical Center Schleswig-Holstein, Campus Lübeck, Germany.

PMID: 27668284
PMCID: PMC5022844
DOI: 10.1212/NXG.0000000000000106

Abstract

Recently, exome sequencing has extended our knowledge of genetic causes of developmental delay through identification of de novo, germline mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) in 13 patients with neurodevelopmental disability and a wide range of additional symptoms and signs including hypotonia in 11 and seizures in 10 of the patients. Limb/arm dystonia was found in 2 patients.(1).

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Figures

**Figure 1.. Pedigree and clinical picture of the patient**
(A) Snapshot of the patient demonstrates dystonic postures of the limbs, trunk, and neck. (B) Pedigree comprises the index patient (filled symbol) and her healthy parents (blank symbols). Results of the validation of the de novo mutation in *GNB1* (c.353A>G, p.D118G) by Sanger sequencing on the reverse strand are shown. Both unaffected parents carry 2 wild-type alleles at the respective position (highlighted by arrow), while the affected daughter is a heterozygous mutation carrier.

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References

1. Petrovski S, Kury S, Myers CT, et al. . Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures. Am J Hum Genet 2016;98:1001–1010. - PMC - PubMed
1. Domingo A, Erro R, Lohmann K. Novel dystonia genes: clues on disease mechanisms and the complexities of high-throughput sequencing. Mov Disord 2016;31:471–477. - PubMed
1. Vissers LE, Gilissen C, Veltman JA. Genetic studies in intellectual disability and related disorders. Nat Rev Genet 2016;17:9–18. - PubMed
1. Fuchs T, Saunders-Pullman R, Masuho I, et al. . Mutations in GNAL cause primary torsion dystonia. Nat Genet 2013;45:88–92. - PMC - PubMed
1. Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB. The 2.0 A crystal structure of a heterotrimeric G protein. Nature 1996;379:311–319. - PubMed

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[1] Petrovski S, Kury S, Myers CT, et al. . Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures. Am J Hum Genet 2016;98:1001–1010. - PMC - PubMed

[2] Petrovski S, Kury S, Myers CT, et al. . Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures. Am J Hum Genet 2016;98:1001–1010. - PMC - PubMed

[3] Domingo A, Erro R, Lohmann K. Novel dystonia genes: clues on disease mechanisms and the complexities of high-throughput sequencing. Mov Disord 2016;31:471–477. - PubMed

[4] Domingo A, Erro R, Lohmann K. Novel dystonia genes: clues on disease mechanisms and the complexities of high-throughput sequencing. Mov Disord 2016;31:471–477. - PubMed

[5] Vissers LE, Gilissen C, Veltman JA. Genetic studies in intellectual disability and related disorders. Nat Rev Genet 2016;17:9–18. - PubMed

[6] Vissers LE, Gilissen C, Veltman JA. Genetic studies in intellectual disability and related disorders. Nat Rev Genet 2016;17:9–18. - PubMed

[7] Fuchs T, Saunders-Pullman R, Masuho I, et al. . Mutations in GNAL cause primary torsion dystonia. Nat Genet 2013;45:88–92. - PMC - PubMed

[8] Fuchs T, Saunders-Pullman R, Masuho I, et al. . Mutations in GNAL cause primary torsion dystonia. Nat Genet 2013;45:88–92. - PMC - PubMed

[9] Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB. The 2.0 A crystal structure of a heterotrimeric G protein. Nature 1996;379:311–319. - PubMed

[10] Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB. The 2.0 A crystal structure of a heterotrimeric G protein. Nature 1996;379:311–319. - PubMed

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Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability

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Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability

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