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A novel phosphoryla...
A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts
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- Ingre, Caroline, 1977- (author)
- Karolinska Institutet,Umeå universitet,Klinisk neurovetenskap,Department of Neurology, The Karolinske University Hospital Huddinge, Stockholm, Sweden,ALS
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Landers, John E. (author)
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Rizik, Naji (author)
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Volk, Alexander E. (author)
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- Akimoto, Chizuru (author)
- Umeå universitet,Klinisk neurovetenskap
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- Birve, Anna (author)
- Umeå universitet,Klinisk neurovetenskap
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Hubers, Annemarie (author)
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Keagle, Pamela J. (author)
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Piotrowska, Katarzyna (author)
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- Press, Rayomand (author)
- Karolinska Institutet
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- Andersen, Peter M. (author)
- Umeå universitet,Klinisk neurovetenskap,Department of Neurology, Ulm University, Ulm, Germany
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Ludolph, Albert C. (author)
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Weishaupt, Jochen H. (author)
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(creator_code:org_t)
- New York : Elsevier, 2013
- 2013
- English.
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In: Neurobiology of Aging. - New York : Elsevier. - 0197-4580 .- 1558-1497. ; 34:6
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https://urn.kb.se/re...
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Abstract
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- Profilin 1 is a central regulator of actin dynamics. Mutations in the gene profilin 1 (PFN1) have veryrecently been shown to be the cause of a subgroup of amyotrophic lateral sclerosis (ALS). Here, weperformed a large screen of US, Nordic, and German familial and sporadic ALS and frontotemporaldementia (FTLD) patients for PFN1 mutations to get further insight into the spectrum and pathogenicrelevance of this gene for the complete ALS/FTLD continuum. Four hundred twelve familial and 260sporadic ALS cases and 16 ALS/FTLD cases from Germany, the Nordic countries, and the United Stateswere screened for PFN1 mutations. Phenotypes of patients carrying PFN1 mutations were studied. Ina German ALS family we identified the novel heterozygous PFN1 mutation p.Thr109Met, which wasabsent in controls. This novel mutation abrogates a phosphorylation site in profilin 1. The recentlydescribed p.Gln117Gly sequence variant was found in another familial ALS patient from the United States.The ALS patients with mutations in PFN1 displayed spinal onset motor neuron disease without overtcognitive involvement. PFN1 mutations were absent in patients with motor neuron disease anddementia, and in patients with only FTLD. We provide further evidence that PFN1 mutations can causeALS as a Mendelian dominant trait. Patients carrying PFN1 mutations reported so far represent the“classic” ALS end of the ALS-FTLD spectrum. The novel p.Thr109Met mutation provides additional proofof-principle that mutant proteins involved in the regulation of cytoskeletal dynamics can cause motorneuron degeneration. Moreover, this new mutation suggests that fine-tuning of actin polymerization byphosphorylation of profilin 1 might be necessary for motor neuron survival.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Geriatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Geriatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Keyword
- Amyotrophic lateral sclerosis
- ALS
- FTLD
- profilin1
- Cytoskeleton
- Actin
- neurologi
- Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Ingre, Caroline, ...
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Landers, John E.
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Rizik, Naji
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Volk, Alexander ...
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Akimoto, Chizuru
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Birve, Anna
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show more...
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Hubers, Annemari ...
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Keagle, Pamela J ...
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Piotrowska, Kata ...
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Press, Rayomand
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Andersen, Peter ...
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Ludolph, Albert ...
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Weishaupt, Joche ...
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Neurobiology of ...
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Umeå University
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Karolinska Institutet