<i>NOTCH2NLC</i>-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor/ataxia syndrome

Ng, Adeline Su Lyn; Xu, Zheyu; Chen, Zhiyong; Tan, Yi Jayne; Lim, Weng Khong; Ting, Simon; Yu, Wai‐Yung; Cheng, Qianhui; Foo, Jia Nee; Tan, Eng King; Lim, Tchoyoson Choie Cheio

doi:10.1093/brain/awaa210

Cited by 11 publications

(5 citation statements)

References 11 publications

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“…They cause a late-onset disorder with a clinical variability that includes muscle weakness, dementia, parkinsonism, tremor, and ataxia. The molecular mechanisms of OTCH2NLC lead to neuronal intranuclear eosinophilic inclusions, and the antisense isoform has been hypothesized to be a pathological mechanism [ 167 ].…”

Section: The Molecular Basis Of Fxpacmentioning

confidence: 99%

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Tassone,

Protic,

Allen

et al. 2023

Cells

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The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

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Section: The Molecular Basis Of Fxpacmentioning

confidence: 99%

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Tassone,

Protic,

Allen

et al. 2023

Cells

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“…These findings are similar to fragile X associated tremor ataxia syndrome, classically identified by bilateral high signal in the middle cerebellar peduncles (MCP) on T2-weighted images, known as the ‘MCP sign’. Some patients with neuronal intranuclear inclusion disease also show the ‘MCP sign’ 8. Other differential diagnoses include white matter diseases such as progressive multifocal leukoencephalopathy, characterised by asymmetric lesions with a predilection for peripheral white matter and subcortical U-fibres, and acute disseminated encephalomyelitis, which has asymmetrical scattered lesions affecting both white and grey matter structures 9.…”

Section: Discussionmentioning

confidence: 99%

Neuronal intranuclear inclusion disease

et al. 2023

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“…2C,D) and also histological findings. 101,113,114 However, it appears that FXTAS is quite rare in Asian populations (Chinese, Japanese, Koreans, and Singaporeans). 2,101 Like most other genetic neurodegenerative disorders, NIID has no specific treatment besides supportive and symptomatic therapy.…”

Section: Dyt/park-pla2g6-related Parkinsonismmentioning

confidence: 99%

Genetic Movement Disorders Commonly Seen in Asians

Jagota

Lim

Pal

et al. 2023

Movement Disord Clin Pract

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The increasing availability of molecular genetic testing has changed the landscape of both genetic research and clinical practice. Not only is the pace of discovery of novel disease-causing genes accelerating but also the phenotypic spectra associated with previously known genes are expanding. These advancements lead to the awareness that some genetic movement disorders may cluster in certain ethnic populations and genetic pleiotropy may result in unique clinical presentations in specific ethnic groups. Thus, the characteristics, genetics and risk factors of movement disorders may differ between populations. Recognition of a particular clinical phenotype, combined with information about the ethnic origin of patients could lead to early and correct diagnosis and assist the development of future personalized medicine for patients with these disorders. Here, the Movement Disorders in Asia Task Force sought to review genetic movement disorders that are commonly seen in Asia, including Wilson's disease, spinocerebellar ataxias (SCA) types 12, 31, and 36, Gerstmann-Sträussler-Scheinker disease, PLA2G6-related parkinsonism, adult-onset neuronal intranuclear inclusion disease (NIID), and paroxysmal kinesigenic dyskinesia. We also review common disorders seen worldwide with specific mutations or presentations that occur frequently in Asians.

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NOTCH2NLC-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor/ataxia syndrome

Cited by 11 publications

References 11 publications

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Neuronal intranuclear inclusion disease

Genetic Movement Disorders Commonly Seen in Asians

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