Wide phenotypic spectrum of the TARDBP gene: homozygosity of A382T mutation in a patient presenting with amyotrophic lateral sclerosis, Parkinson's disease, and frontotemporal lobar degeneration, and in neurologically healthy subject

Mosca, Lorena; Lunetta, Christian; Tarlarini, Claudia; Avemaria, Francesca; Maestri, Eleonora; Melazzini, Mario; Corbo, Massimo; Penco, Silvana

doi:10.1016/j.neurobiolaging.2012.01.108

Cited by 44 publications

(32 citation statements)

References 18 publications

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“…Neuroprotective action of oestrogens has been recognised in Parkinson's disease as well,25 which suggests several analogies with ALS. ALS and Parkinson's disease may share a common genetic mutation in TARDBP, vulnerability for FTD and analogies in clinical features 26 27. This oestrogen action may explain, in terms of gonadal hormones neuroprotection, the predominance of ALS in males in younger age groups, as described in the literature, whereas the risk of ALS is reported to be the same for males and females after menopause.…”

Section: Discussionmentioning

confidence: 83%

Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients

Palmieri

Mento

Calvo

et al. 2014

J Neurol Neurosurg Psychiatry

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Results highlight a significant vulnerability of ALS female patients to develop cognitive dysfunctions peculiar to the disease, independently of bulbar onset. The explicative hypotheses of the data are focused on two interpretative lines not mutually exclusive: the role of gonadal hormones and gender-related brain asymmetry pre-existing to the disease. These findings, never reported before in the literature, can have important implications for models of ALS pathogenesis and for future clinical trial designs.

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Section: Discussionmentioning

confidence: 83%

Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients

Palmieri

Mento

Calvo

et al. 2014

J Neurol Neurosurg Psychiatry

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“…The TARDBP gene, located on chromosome 1p36.22, encodes a 43-kDa ubiquitously expressed nuclear DNA- and RNA-binding protein (TDP-43) [62]. To date, more than 30 TARDBP mutations have been reported, which explains approximately 4% of familial ALS cases and a smaller proportion of FTD cases [63]. The mode of inheritance is autosomal dominant.…”

Section: Clinical Genetics General Characteristic and Parkinsonimentioning

confidence: 99%

Parkinsonian syndrome in familial frontotemporal dementia

Siuda¹,

Fujioka²,

Wszołek³

2014

Parkinsonism & Related Disorders

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Parkinsonism in frontotemporal dementia (FTD) was first described in families with mutations in the microtubule-associated protein tau (MAPT) and progranulin (PRGN) genes. Since then, mutations in several other genes have been identified for FTD with Parkinsonism, including chromosome 9 open reading frame 72 (C9ORF72), chromatin modifying protein 2B (CHMP2B), valosin-containing protein (VCP), fused in sarcoma (FUS) and transactive DNA-binding protein (TARDBP). The clinical presentation of patients with familial forms of FTD with Parkinsonism is highly variable. The Parkinsonism seen in FTD patients is usually characterized by akinetic-rigid syndrome and is mostly associated with the behavioral variant of FTD (bvFTD); however, some cases may present with classical Parkinson’s disease. In other cases, atypical Parkinsonism resembling progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS) has also been described. Although rare, Parkinsonism in FTD may coexist with motor neuron disease. Structural neuroimaging, which is crucial for the diagnosis of FTD, shows characteristic patterns of brain atrophy associated with specific mutations. Structural neuroimaging is not helpful in distinguishing among patients with parkinsonian features. Furthermore, dopaminergic imaging that shows nigrostriatal neurodegeneration in FTD with Parkinsonism cannot discriminate parkinsonian syndromes that arise from different mutations. Generally, Parkinsonism in FTD is levodopa unresponsive, but there have been cases where a temporary benefit has been reported, so dopaminergic treatment is worth trying, especially, when motor and non-motor manifestations can cause significant problems with daily functioning. In this review, we present an update on the clinical and genetic correlations of FTD with Parkinsonism.

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“…This pathologic TDP-43 is one of the primary components of ubiquitin-positive inclusions in the affected brain and spinal cord regions of patients with FTLD and ALS (Neumann et al, 2006). In addition, TDP-43 pathology has been detected in Parkinson's disease, dementia with Lewy bodies, and AD cases (Amador-Ortiz et al, 2007;Bigio, 2008;Higashi et al, 2007;Mishra et al, 2007;Mosca et al, 2012;Uryu et al, 2008;Wang et al, 2008). Neurodegenerative diseases characterized by pathologic TDP-43 are described as TDP-43 proteinopathies (Armstrong et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse

Liu

Atkinson

Fernández-Martos

et al. 2015

Neurobiology of Aging

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Wide phenotypic spectrum of the TARDBP gene: homozygosity of A382T mutation in a patient presenting with amyotrophic lateral sclerosis, Parkinson's disease, and frontotemporal lobar degeneration, and in neurologically healthy subject

Cited by 44 publications

References 18 publications

Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients

Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients

Parkinsonian syndrome in familial frontotemporal dementia

Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse

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