| 3. |
- Dulski, J., et al.
(författare)
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Neuroacanthocytosis - Clinical variability (a report on six cases)
- 2014
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 29:Suppl 1, s. 194-194
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Konferensbidrag (refereegranskat)abstract
- Objective: To provide clinical clues to differential diagnosis in patients with chorea and other movement disorders with blood acanthocytes. Background: Neuroacanthocytosis (NA) is an umbrella term for neurological conditions associated with acanthocytosis. Core NA syndromes, with basal ganglia involvement and in which acanthocytosis is a frequent finding, include autosomal recessive choreaacanthocytosis (Ch-Ac) and X-linked McLeod syndrome (MLS). Due to the very low prevalence, scarcity of data and high clinical variability they may be underdiagnosed. Methods: Six male patients (pts), three diagnosed with Ch-Ac: 33-y.o.(no.1), 35-y.o.(no.2), 42-y.o.(no.3), two diagnosed with MLS: 52-y.o.(no.4), 60-y.o.(no.5) and one 62-y.o.(no.6), a brother of no.5, with clinical suspicion of MLS. The patients had an unremarkable family history and were asymptomatic until adulthood. Pts no.1,2,4,5,6 developed generalized chorea and patient no.3 had predominant bradykinesia. Pts no.1,2,3 had phonic and motor tics, additionally pts no.1 and 2 exhibited peculiar oromandibular dystonia with tongue thrusting. In pts no.2 and 3 dystonic supination of feet was observed, patient no.3 subsequently developed bilateral foot drop. Pts no. 2 and 4 had signs of muscle atrophy. Tendon reflexes were decreased or absent and electroneurography demonstrated sensorimotor neuropathy in patients no. 1,2,3,4,5, except no. 6. Generalized seizures were seen in patients no.2,3,5,6 and myoclonic jerks in patient no 1. Cognitive deterioration was reported in patients no.1,2,3,5,6. Serum creatine kinase levels were elevated in all six patients. Results: Peripheral blood smears revealed acanthocytosis in patients no.1,2,3,5,6, except no. 4. In patients no. 1 and 3 reduced expression of chorein was detected on Western blot. In patient no. 2 genetic testing showed mutations in VPS13A gene and in no.4 and 5 genetic analysis confirmed mutations in XK gene (MLS). The time from the onset of symptoms till establishing the diagnosis in patients no. 1,2,3,4,5 was 11,5,7,6,32 years respectively. Patient no.4 suddenly developed multiple organ failure and died of cardiac arrhythmia at the age of 52. Conclusions: We highlight the variability of clinical presentation of NA syndromes and the long time from the onset to diagnosis with the need to screen the blood smears in uncertain cases, however, as in one of our cases acanthocytes may even be not found.
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| 4. |
- Sitek, E. J., et al.
(författare)
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A Patient with Posterior Cortical Atrophy Possesses a Novel Mutation in the Presenilin 1 Gene
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Posterior cortical atrophy is a dementia syndrome with symptoms of cortical visual dysfunction, associated with amyloid plaques and neurofibrillary tangles predominantly affecting visual association cortex. Most patients diagnosed with posterior cortical atrophy will finally develop a typical Alzheimer's disease. However, there are a variety of neuropathological processes, which could lead towards a clinical presentation of posterior cortical atrophy. Mutations in the presenilin 1 gene, affecting the function of gamma-secretase, are the most common genetic cause of familial, early-onset Alzheimer's disease. Here we present a patient with a clinical diagnosis of posterior cortical atrophy who harbors a novel Presenilin 1 mutation (I211M). In silico analysis predicts that the mutation could influence the interaction between presenilin 1 and presenilin1 enhancer-2 protein, a protein partner within the gamma-secretase complex. These findings along with published literature support the inclusion of posterior cortical atrophy on the Alzheimer's disease spectrum.
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