Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44

Watson, Lauren M.; Bamber, Elizabeth; Schnekenberg, Ricardo Parolin; Williams, Jonathan M. J.; Bettencourt, Conceição; Lickiss, Jennifer; Jayawant, Sandeep; Fawcett, Katherine A.; Clokie, Samuel; Wallis, Yvonne; Clouston, Penny; Sims, David; Houlden, Henry; Becker, Esther B. E.; Németh, Andrea H.

doi:10.1016/j.ajhg.2017.10.008

Cited by 25 publications

(24 citation statements)

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“…On the other hand, a gene that encodes the Glutamate , and GRIN2C (Z-score 1.85). GRM1 is one of the most abundant mGluRs in the mammalian central nervous system and is present at particularly high levels in Purkinje cells [69]. There is plenty of evidence of its implication in diseases involving glutamatergic dysfunction and abnormal synaptic plasticity [70], which are known to be crucial mechanisms for cognitive processes.…”

Section: Temporal and Spatial Gene Expression In Postmortem Brains Ofmentioning

confidence: 99%

Temporal and Spatial Differential Expression of Glutamate Receptor Genes in the Brain of Down Syndrome

Ortiz¹,

Saldarriaga²,

Villegas³

et al. 2019

Gene Regulation

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Studying the dysregulation of expression of glutamate receptors is crucial to better understand the mechanisms associated with cognitive disabilities in Down syndrome (DS) patients. By using data of microarray experiments previously deposited in GEO Dataset, we studied the expression of 26 glutamate receptor genes in DS brain samples since prenatal to adult age in several brain structures. Overall, our results showed a complexity in the expression of the genes which were dependent mainly on the brain structure analyzed; especially, the hippocampus showed a different expression pattern. While in the general brain analysis the overexpressed genes were GRIN3A and GRIN2C, higher expression levels of GRM1, GRID2, and GRIK1 gene receptors were recorded in hippocampus. Our results suggest that the glutamatergic system in association with other neurotransmitter systems in the human brain would associate with glutamatergic receptor alterations to bring upon synaptic changes and cognitive deficits in DS models.

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Section: Temporal and Spatial Gene Expression In Postmortem Brains Ofmentioning

confidence: 99%

Temporal and Spatial Differential Expression of Glutamate Receptor Genes in the Brain of Down Syndrome

Ortiz¹,

Saldarriaga²,

Villegas³

et al. 2019

Gene Regulation

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show abstract

“…Genes causing SCAs code for a large variety of proteins including ion channels (Riess et al, 1997;Zhuchenko et al, 1997;Waters et al, 2006;Lee et al, 2012;Coutelier et al, 2015;Fogel et al, 2015;Morino et al, 2015), transcription factors and repressors (Orr et al, 1993;Koide et al, 1999;Lin et al, 2018), scaffolding proteins (Ikeda et al, 2006;Tsoi et al, 2014), or signaling kinases (Chen et al, 2003;Houlden et al, 2007), phosphatases (Holmes et al, 1999), and receptors (Storey et al, 2001;Hara et al, 2004;Hara et al, 2008;Huang et al, 2012;Watson et al, 2017). Despite this heterogeneity, SCA patients share a slow dramatic degeneration of the cerebellum and its afferent and efferent systems, suggesting a common point of interception, wherein SCA causing mutations converge and promotes the onset of these neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Cerebellar Development and Circuit Maturation: A Common Framework for Spinocerebellar Ataxias

2020

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“…Besides the polyQ group, diseasecausing repeat expansions have been identified in non-coding regions of the gene in some SCAs (SCA8, 10,12,31,36,37) similarly to Friedreich ataxia, which is the most common autosomal recessive cerebellar ataxia (Table 2) [4,5]. Moreover, conventional mutations (point mutations, deletions, insertions) can cause certain types of SCA, including SCA5, 11, 13, 14, 15/16, 19/22, 21, 23, 26-29, 34, 35, 38, 40-47 (Table 3) [4][5][6][7][8][9], whereas in some forms of SCA, including SCA4, 18, 20, 25, 30 and 32 only the genetic loci, but not the responsible gene, have been identified.…”

Section: Introductionmentioning

confidence: 99%

Clinical Characteristics and Possible Drug Targets in Autosomal Dominant Spinocerebellar Ataxias

Szpisjak

Zádori

Klivényi

et al. 2019

CNSNDDT

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Background & Objective: The autosomal dominant spinocerebellar ataxias (SCAs) belong to a large and expanding group of neurodegenerative disorders. SCAs comprise more than 40 subtypes characterized by progressive ataxia as a common feature. The most prevalent diseases among SCAs are caused by CAG repeat expansions in the coding-region of the causative gene resulting in polyglutamine (polyQ) tract formation in the encoded protein. Unfortunately, there is no approved therapy to treat cerebellar motor dysfunction in SCA patients. In recent years, several studies have been conducted to recognize the clinical and pathophysiological aspects of the polyQ SCAs more accurately. This scientific progress has provided new opportunities to develop promising gene therapies, including RNA interference and antisense oligonucleotides. Conclusion: The aim of the current work is to give a brief summary of the clinical features of SCAs and to review the cardinal points of pathomechanisms of the most common polyQ SCAs. In addition, we review the last few year’s promising gene suppression therapies of the most frequent polyQ SCAs in animal models, on the basis of which human trials may be initiated in the near future.

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Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44

Abstract: In Figure 1C, the substitution ''p.Tyr792Cys'' incorrectly appeared as ''p.Tyr292Cys.'' This error has been corrected online. The authors regret this mistake.

Cited by 25 publications

References 0 publications

Temporal and Spatial Differential Expression of Glutamate Receptor Genes in the Brain of Down Syndrome

Temporal and Spatial Differential Expression of Glutamate Receptor Genes in the Brain of Down Syndrome

Cerebellar Development and Circuit Maturation: A Common Framework for Spinocerebellar Ataxias

Clinical Characteristics and Possible Drug Targets in Autosomal Dominant Spinocerebellar Ataxias

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