Role of ANO3 mutations in dystonia: A large-scale mutational screening study

Olschewski, Luisa; Jesús, Silvia; Kim, Han Joon; Tunc, Sinem; Löns, Sebastian; Junker, Johanna; Zeuner, Kirsten E.; Kühn, Andrea A.; Kuhlenbäumer, Gregor; Schäffer, Eva; Berg, Daniela; Kasten, Meike; Ferbert, A.; Altenmüller, Eckart; Brüggemann, Norbert; Bauer, Péter; Rolfs, Arndt; Jeon, Beomseok; Bäumer, Tobias; Mir, Pablo; Klein, Christine; Lohmann, Katja

doi:10.1016/j.parkreldis.2018.12.030

Cited by 26 publications

(31 citation statements)

References 12 publications

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“…To date, there have been at least 5 reported cases documenting a response to bilateral GPi-DBS in ANO3-related dystonia (96)(97)(98)(99)(100). For example, one patient with a de novo variant in ANO3 (p.Val561Glu) and early onset, generalized dystonia was found to improve with bilateral GPi-DBS, resulting in a sustained benefit allowing her to walk with assistance (99). Another patient with an ANO3 mutation (p.Glu510Lys) had a substantial improvement in dystonia and tremor but in this case myoclonus persisted (96).…”

Section: Dyt-ano3 (Dyt24)mentioning

confidence: 99%

Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome

Tisch

Kumar

2021

Front. Neurol.

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Globus pallidus internus deep brain stimulation (GPi DBS) is the most effective intervention for medically refractory segmental and generalized dystonia in both children and adults. Predictive factors for the degree of improvement after GPi DBS include shorter disease duration and dystonia subtype with idiopathic isolated dystonia usually responding better than acquired combined dystonias. Other factors contributing to variability in outcome may include body distribution, pattern of dystonia and DBS related factors such as lead placement and stimulation parameters. The responsiveness to DBS appears to vary between different monogenic forms of dystonia, with some improving more than others. The first observation in this regard was reports of superior DBS outcomes in DYT-TOR1A (DYT1) dystonia, although other studies have found no difference. Recently a subgroup with young onset DYT-TOR1A, more rapid progression and secondary worsening after effective GPi DBS, has been described. Myoclonus dystonia due to DYT-SCGE (DYT11) usually responds well to GPi DBS. Good outcomes following GPi DBS have also been documented in X-linked dystonia Parkinsonism (DYT3). In contrast, poorer, more variable DBS outcomes have been reported in DYT-THAP1 (DYT6) including a recent larger series. The outcome of GPi DBS in other monogenic isolated and combined dystonias including DYT-GNAL (DYT25), DYT-KMT2B (DYT28), DYT-ATP1A3 (DYT12), and DYT-ANO3 (DYT24) have been reported with varying results in smaller numbers of patients. In this article the available evidence for long term GPi DBS outcome between different genetic dystonias is reviewed to reappraise popular perceptions of expected outcomes and revisit whether genetic diagnosis may assist in predicting DBS outcome.

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Section: Dyt-ano3 (Dyt24)mentioning

confidence: 99%

Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome

Tisch

Kumar

2021

Front. Neurol.

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“…Of these ~200 dystonia genes, 7 3 were listed as isolated dystonia genes by the MDS Task force on Genetic Nomenclature in Movement Disorders in 2016 3 : TOR1A , THAP1 , and GNAL . Meanwhile, there is increasing evidence for a pathogenic role of ANO3 variants, particularly because of the identification of de novo mutations 7,8 . Mutations in PRKRA were initially reported as a cause of a combined dystonia (dystonia‐parkinsonism, DYT16) 9 .…”

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confidence: 99%

Genotype–Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review

et al. 2021

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A BS TRACT: This comprehensive MDSGene review is devoted to 7 genes -TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCAmutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of~1200 citations. Phenotypic and genotypic data on~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics.

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“…We present a patient with generalized dystonia due to a novel mutation in the ANO3 gene and the long-term response to DBS. This is, to our knowledge, only the second genetically confirmed case of ANO3 dystonia to be treated with DBS, besides the one briefly mentioned in the paper by Olschewski et al [5].…”

mentioning

confidence: 74%

“…More recently, mutations in the anoctamin-3 gene ( ANO3 , OMIM 610110, DYT 24) have also been implicated as the cause of autosomal dominant dystonia. The phenotypic spectrum of this condition is broad, ranging from cranio-cervical dystonia [1] with tremor, upper limb dystonia [2], lower limb dystonia [3], blepharospasm, myoclonus dystonia, and dystonia-parkinsonism [4] typically with age at onset between the 3 rd and 5 th decade of life [5], although children with ANO3 mutations have been described. The presence of tremor may help differentiate ANO3 from dystonia due to mutations in the GNAL gene.…”

mentioning

confidence: 99%

Successful Pallidal Deep Brain Stimulation Treatment in a Case of Generalized Dystonia due to a Novel ANO3 Mutation

Lasky

Bliss

Sidiropoulos

2019

Case Reports in Neurological Medicine

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Background Dystonia is a ubiquitous syndrome, with a growing number of genes being continually identified. Mutations in the anoctamin-3 gene have been described to cause dystonia but the management and long-term outcomes are still largely unknown. Methods We present here a long term, longitudinal follow up of a patient with generalized dystonia, who was treated with bilateral pallidal deep brain stimulation and was found to harbor a mutation in the anoctamin-3 gene. Results Ongoing adjustment of stimulation settings and medications led to good and sustained dystonia control; however the patient did suffer short term relapses, manifested as dystonic crisis, which necessitated inpatient admission. Conclusion This only the second patient to be reported with pallidal stimulation and an anoctamin-3 gene mutation. Long term outcomes seem to be favorable but larger case series are needed to confirm our findings.

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Role of ANO3 mutations in dystonia: A large-scale mutational screening study

Cited by 26 publications

References 12 publications

Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome

Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome

Genotype–Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review

Successful Pallidal Deep Brain Stimulation Treatment in a Case of Generalized Dystonia due to a Novel ANO3 Mutation

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