Frequency of FMR1 premutation in individuals with ataxia and/or tremorand/or parkinsonism

Reis, A. H. O.; Ferreira, Andressa Coelho; Gomes, Karina Braga; Aguiar, Marcos José Burle de; Fonseca, Carmen; Cardoso, F. E.; Pardini, Victor Cavalcanti; Carvalho, Maria Raquel Santos

doi:10.4238/vol7-1gmr357

Cited by 22 publications

(15 citation statements)

References 44 publications

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“…A subsequent study, which compared 903 Caucasian males with either early and late onset PD or essential tremor to earlier population norms from French Canadians, also reported no significant excess of GZ allele (45–54) carriers . One other study compared only 66 male patients (with non‐specified parkinsonism) to 74 normal controls from the same population and, again, reported no association .…”

Section: Discussionmentioning

confidence: 92%

New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

Loesch

Tassone

et al. 2012

Clinical Genetics

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We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ-carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.

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Section: Discussionmentioning

confidence: 92%

New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

Loesch

Tassone

et al. 2012

Clinical Genetics

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“…MRI can show hyperintensities of the medial cerebellar peduncle and within the corpus callosum [47]. We have reviewed eight studies that sought to address the frequency of the FMR1 premutation in patients with unexplained ataxia [48][49][50][51][52][53][54][55]. In a recent study of 22 patients with FXTAS, 43% had a negative family history [18].…”

Section: Recommendationmentioning

confidence: 99%

EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood

Warrenburg

Gaalen

Boesch

et al. 2014

Euro J of Neurology

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Background and objectives The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer‐reviewed evidence‐based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia. Methods This guideline is based on systematic evaluations of the relevant literature and on three consensus meetings of the task force. Diagnosis If acquired causes are ruled out, and if the disease course is rather slowly progressive, a (heredo)degenerative disease is likely. A positive family history gives much guidance. In the case of a dominant family history, first line genetic screening is recommended for spinocerebellar ataxia (SCA) 1, 2, 3, 6, 7 and 17 (level B), and in Asian patients also for dentatorubral‐pallidoluysian atrophy (DRPLA). In the case of recessive disease, a stepwise diagnostic work‐up is recommended, including both biochemical markers and targeted genetic testing, particularly aimed at Friedreich's ataxia, ataxia telangiectasia, ataxia due to vitamin E deficiency, polymerase gamma gene (POLG gene, various mutations), autosomal recessive spastic ataxia of Charlevoix−Saguenay (ARSACS) and ataxia with oculomotor apraxia (AOA) types 1 and 2. If family history is negative, we still advise to screen for the more common dominant and recessive ataxias. In addition, if onset is below 45 years we recommend the full work‐up for recessive ataxias; if onset is above 45 years we recommend to screen for fragile X mental retardation 1 FMR1 premutations (good practice points). In sporadic cases with an onset after 30 years, a diagnosis of multiple system atrophy should be considered (good practice point). In particular the genetic work‐up will change over the upcoming years due to the diagnostic utility of new techniques such as gene panel diagnostics based on next generation sequencing for routine work‐up, or even whole exome and genome sequencing for selected cases. Treatment Some of the rare recessive ataxias are treatable, but for most of the heredodegenerative ataxias treatment is purely symptomatic. Idebenone is not effective in Friedreich's ataxia (level A). Riluzole (level B) and amantadine (level C) might provide symptomatic relief, irrespective of exact etiology. Also, varenicline for SCA3 patients (level B) can be considered. There is level Class II evidence to recommend physiotherapy, and Class III data to support occupational therapy.

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“…Associated clinical features of FXTAS include cognitive decline, Parkinsonism, peripheral neuropathy, and autonomic dysfunction [23, 35, 36, 38, 46, 54, 55, 61, 67, 77]. The neuropathological hallmark of FXTAS is the presence of eosinophilic, ubiquitin-positive intranuclear inclusions in both neurons and astroglia throughout brain upon post mortem histological analysis [30–34, 77].…”

Section: Introductionmentioning

confidence: 99%

Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice

et al. 2011

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder generally presenting with intention tremor and gait ataxia, but with a growing list of co-morbid medical conditions including hypothyroidism, hypertension, peripheral neuropathy, and cognitive decline. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in both neurons and astroglia. However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS). To address this issue, we surveyed non-CNS organs in ten human cases with FXTAS and in a CGG repeat knock-in (CGG KI) mouse model known to possess neuronal and astroglial inclusions. We find inclusions in multiple tissues from FXTAS cases and CGG KI mice, including pancreas, thyroid, adrenal gland, gastrointestinal, pituitary gland, pineal gland, heart, and mitral valve, as well as throughout the associated autonomic ganglia. Inclusions were observed in the testes, epididymis, and kidney of FXTAS cases, but were not observed in mice. These observations demonstrate extensive involvement of the peripheral nervous system and systemic organs. The finding of intranuclear inclusions in non-CNS somaticorgan systems, throughout the PNS, and in the enteric nervous system of both FXTAS cases as well as CGG KI mice suggests that these tissues may serve as potential sites to evaluate early intervention strategies or be used as diagnostic factors.

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Frequency of FMR1 premutation in individuals with ataxia and/or tremorand/or parkinsonism

Cited by 22 publications

References 44 publications

New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood

Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice

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