Premutations in the <i>FMR1</i> gene as a modifying factor in <i>Parkin</i>‐associated Parkinson's disease?

Hedrich, Katja; Pramstaller, Peter P.; Stübke, Katrin; Hiller, Anja; Kabakci, Kemal; Purmann, Sabine; Kasten, Meike; Scaglione, Cesa; Schwinger, E.; Volkmann, Jens; Kostić, Vladimir; Vieregge, P.; Martinelli, Paolo; Abbruzzese, Giovanni; Klein, Christine; Zühlke, Christine

doi:10.1002/mds.20512

Cited by 32 publications

(24 citation statements)

References 11 publications

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“…As has been pointed out previously,88 the results of these screening studies yielded smaller prevalence rates than expected. These studies likely underestimate the true contribution of the FMR1 premutation in movement disorders for a number of reasons.…”

Section: Fxtas Screening In Movement Disorders Cohortssupporting

confidence: 62%

Fragile X‐associated tremor/ataxia syndrome: Clinical features, genetics, and testing guidelines

et al. 2007

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55-200 repeats; premutation range) of a CGG trinucleotide in the fragile X mental retardation 1 (FMR1) gene, the same gene which causes fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made.

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Section: Fxtas Screening In Movement Disorders Cohortssupporting

confidence: 62%

Fragile X‐associated tremor/ataxia syndrome: Clinical features, genetics, and testing guidelines

et al. 2007

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“…These mutations are present not only in the homozygous or compound heterozygous state, compatible with recessive transmission, but also, in a substantial number of cases, as single heterozygous mutations. It is unknown whether single heterozygous parkin mutations are themselves pathogenic, whether a second mutation may have been missed during screening, or whether there are epistatic interactions with mutations in other causative genes 7 – 10. The pathogenic role of heterozygous mutations remains, therefore, a matter of debate.…”

mentioning

confidence: 99%

Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls

Lesage¹,

Lohmann²,

Tison³

et al. 2007

Journal of Medical Genetics

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“…This represents an improvement for many men with FXTAS who are misdiagnosed as having Parkinson’s, other ataxias, stroke, Alzheimer’s, multiple sclerosis and other movement disorders [Hall et al, 2005; Hedrich et al, 2005]. …”

Section: Discussionmentioning

confidence: 99%

Newborn screening and cascade testing for FMR1 mutations

Sorensen

Gane

Yarborough

et al. 2012

American J of Med Genetics Pt A

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We describe an ongoing pilot project in which newborn screening (NBS) for FMR1 mutations and subsequent cascade testing are performed by the MIND Institute at the University of California, Davis Medical Center (UCDMC). To date, out of 3042 newborns initially screened, 44 extended family members have been screened by cascade testing of extended family members once a newborn is identified. 14 newborns (7 males and 7 females) and 27 extended family members (5 males and 22 females) have been identified with FMR1 mutations. Three family histories are discussed in detail, each demonstrating some benefits and risks of NBS and cascade testing for FMR1 mutations in extended family members. While we acknowledge inherent risks, we propose that with genetic counseling, clinical follow-up of identified individuals and cascade testing, newborn screening (NBS) has significant benefits. Treatment for individuals in the extended family who would otherwise not have received treatment can be beneficial. In addition, knowledge of carrier status can lead to lifestyle changes and prophylactic interventions that are likely to reduce the risk of late onset neurological or psychiatric problems in carriers. Also with identification of carrier family members through NBS, reproductive choices become available to those who would not have known that they were at risk to have offspring with fragile X syndrome.

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Premutations in the FMR1 gene as a modifying factor in Parkin‐associated Parkinson's disease?

Cited by 32 publications

References 11 publications

Fragile X‐associated tremor/ataxia syndrome: Clinical features, genetics, and testing guidelines

Fragile X‐associated tremor/ataxia syndrome: Clinical features, genetics, and testing guidelines

Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls

Newborn screening and cascade testing for FMR1 mutations

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