ACTB gene mutation in combined Dystonia-Deafness syndrome with parkinsonism: Expanding the phenotype and highlighting the long-term GPi DBS outcome

Straccia, Giulia; Reale, Chiara; Castellani, Massimo; Colangelo, Isabel; Orunesu, Eva; Meoni, Sara; Moro, Elena; Krack, Paul; Prokisch, Holger; Zech, Michael; Romito, Luigi; Garavaglia, Barbara

doi:10.1016/j.parkreldis.2022.09.012

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…With increasing use of DBS (most commonly targeting the globus pallidus pars internus – GPi), there have been multiple observations that DBS is more effective in children with monogenic forms of dystonia or dyskinesia (particularly TOR1A [67], GNAO1 [68] and KMT2B [69]). In addition, there is emerging evidence for a positive response to GPi DBS in an evolving number of other rare childhood-onset movement disorders ( ACTB [70], ADCY5 [71], ANO3 [72], EIF2AK2 [73], PANK2 [74], SGCE [75], TAF1 [76], THAP1 [77], UBA5 [78]). Independent of cause, an important application of DBS is in the setting of status dystonicus and refractory status dystonicus [79 ▪▪ ,80,81].…”

Section: Deep Brain Stimulationmentioning

confidence: 99%

Emerging therapies for childhood-onset movement disorders

Vogt,

Quiroz,

Ebrahimi-Fakhari

2024

Current Opinion in Pediatrics

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Purpose of review We highlight novel and emerging therapies in the treatment of childhood-onset movement disorders. We structured this review by therapeutic entity (small molecule drugs, RNA-targeted therapeutics, gene replacement therapy, and neuromodulation), recognizing that there are two main approaches to treatment: symptomatic (based on phenomenology) and molecular mechanism-based therapy or ‘precision medicine’ (which is disease-modifying). Recent findings We highlight reports of new small molecule drugs for Tourette syndrome, Friedreich's ataxia and Rett syndrome. We also discuss developments in gene therapy for aromatic l-amino acid decarboxylase deficiency and hereditary spastic paraplegia, as well as current work exploring optimization of deep brain stimulation and lesioning with focused ultrasound. Summary Childhood-onset movement disorders have traditionally been treated symptomatically based on phenomenology, but focus has recently shifted toward targeted molecular mechanism-based therapeutics. The development of precision therapies is driven by increasing capabilities for genetic testing and a better delineation of the underlying disease mechanisms. We highlight novel and exciting approaches to the treatment of genetic childhood-onset movement disorders while also discussing general challenges in therapy development for rare diseases. We provide a framework for molecular mechanism-based treatment approaches, a summary of specific treatments for various movement disorders, and a clinical trial readiness framework.

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Section: Deep Brain Stimulationmentioning

confidence: 99%

Emerging therapies for childhood-onset movement disorders

Vogt,

Quiroz,

Ebrahimi-Fakhari

2024

Current Opinion in Pediatrics

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“…To date, 19 variant-related phenotypes are described. The most frequently encountered variant is c.547C > T (p.Arg183Trp), reported in six clinical studies [ 15 , 16 , 17 , 18 , 19 , 20 ]. This variant and the variants c.484A> G (p.Thr162Ala) [ 20 ], c.586C > T (p.Arg196Cys) (in one out of two case reports) [ 12 , 21 ] and c.826G > A (p.Glu276Lys) [ 22 ], are associated with a hearing impairment.…”

Section: Hearing Loss In Baraitser–winter Syndrome: Evidence Synthesismentioning

confidence: 99%

“…The use of hearing aids for auditory rehabilitation (specifically, a CI) is only reported in the paper by Skogseid et al [15]. Finally, in most patients with the c.547C > T variant, the presence of dystonia, facial dysmorphisms, motor and language delays, renal and genital anomalies and, in only a few cases, motor and step acquisition delay, epilepsy and mild intellectual disability are described [15][16][17][18][19][20]. Audiometric tests are reported in the cases with the variants c.220 G > A (p.Gly74Ser), c.359C4T (p.Thr120Ile) and c.617G > A (p.Arg206Gl), but no hearing impairment was found [12,23. No information on hearing ability or whether it was assessed was reported in any of the remaining clinical reports.…”

Section: Hearing Loss In Baraitser-winter Syndrome: Evidence Synthesismentioning

confidence: 99%

Hearing Loss in Baraitser–Winter Syndrome: Case Reports and Review of the Literature

Ghiselli,

Parmeggiani,

Zambonini

et al. 2024

JCM

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Background: Baraitser–Winter Syndrome (BRWS) is a rare autosomal dominant condition associated with hearing loss (HL). In the literature, two types of this condition are reported, Baraitser–Winter type 1 (BRWS1) and type 2 (BRWS2) produced by specific pathogenetic variants of two different genes, ACTB for BRWS1 and ACTG1 for BRWS2. In addition to syndromic BRWS2, some pathogenic variants in ACTG1 are associated also to another pathologic entity, the “Autosomal dominant non-syndromic hearing loss 20/26”. In these syndromes, typical craniofacial features, sensory impairment (vision and hearing) and intellectual disabilities are frequently present. Heart anomalies, renal and gastrointestinal involvement and seizure are also common. Wide inter- and intra-familial variety in the phenotypic spectrum is reported. Some phenotypic aspects of these syndromes are not yet fully described, such as the degree and progression of HL, and better knowledge of them could be useful for correct follow-up and treatment. Methods and Results: In this study, we report two cases of children with HL and diagnosis of BRWS and a review of the current literature on HL in these syndromes.

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“…The researchers found that when RPS3A was added to yeast cells expressing α-synuclein, the protein was less likely to aggregate and caused less toxicity to the cells. ACTB, cytoplasmic beta actin is associated with early-onset severe deafness-dystonia syndrome, craniofacial dysmorphism [30].…”

Section: Genes Of Interest During Control To Stagementioning

confidence: 99%

Identifying Stage-Specific Genes in Disease Progression using Transition Centrality on Disease Temporal Graphs

Sahu,

2023

Preprint

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The search for biomarkers of diseases has traditionally involved analyzing disease data as a whole. But this approach has largely ignored the significance of disease progression at different stages. Acknowledging the fact that different genes may be responsible for disease progression in different stages, we have developed a novel approach to analyse the temporal graphs that employs a modified version of betweenness centrality, known as ''transition centrality''. Applying this measure to the stage-wise data of three common diseases, namely Alzheimer's disease, Parkinson's disease, and Human breast cancer, we identified successfully a set of genes that may be key players in disease progression. The findings reveal that stage-specific genes can be identified using transition centrality as the specificity of these genes in a particular stage was validated through an extensive review of the relevant literature. Remarkably, this analysis yielded a number of promising disease-related genes for each of the diseases that have been studied, such as RARA and NOS1 in Alzheimer's disease, LRRK2 in Parkinson's disease, and BRCA1, ACTB, TYMS, and many others in human breast cancer. Our results demonstrate that the transition centrality analysis can be utilized to identify stage-specific genes of diseases.

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ACTB gene mutation in combined Dystonia-Deafness syndrome with parkinsonism: Expanding the phenotype and highlighting the long-term GPi DBS outcome

Cited by 5 publications

References 7 publications

Emerging therapies for childhood-onset movement disorders

Emerging therapies for childhood-onset movement disorders

Hearing Loss in Baraitser–Winter Syndrome: Case Reports and Review of the Literature

Identifying Stage-Specific Genes in Disease Progression using Transition Centrality on Disease Temporal Graphs

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