A novel PSEN2 mutation associated with a peculiar phenotype

Istituto Superiore di Sanità, 00161 Rome, Italy.
Neurology (Impact Factor: 8.29). 05/2008; 70(17):1549-54. DOI: 10.1212/01.wnl.0000310643.53587.87
Source: PubMed


Mutations of presenilin 2 gene are a rare cause of familial Alzheimer disease (AD). We describe an Italian family with hereditary dementia associated with a novel mutation in the presenilin 2 gene.
Clinical investigations of the diseased subjects; interviews with relatives; studies of medical records; pedigree analysis; and neuroradiologic, neuropathologic, and molecular genetic studies were carried out in the pedigree.
Genetic analysis showed a novel PSEN2 A85V mutation present in the proband and in all analyzed affected members, in a subject presenting with an amnesic mild cognitive impairment, and in a young, still asymptomatic subject. The proband showed a clinical phenotype indicative of Lewy body dementia and the neuropathologic examination demonstrated the presence of unusually abundant and widespread cortical Lewy bodies in addition to the hallmark lesions of AD. Other affected members exhibited a clinical phenotype typical of AD.
Our findings add complexity to the spectrum of atypical phenotypes associated with presenilin mutations and should then be taken into account when considering the nosography of neurodegenerative diseases. They also support previous data that specific mutations of genes associated with familial Alzheimer disease may influence the presence and extent of Lewy bodies.

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Available from: Annamaria Confaloni
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    • "PSEN1 phenotypes also include extrapyramidal, pyramidal, or cerebellar isolated presentation, rarer in PSEN2 or APP-mutated patients (Table 1). However, prominent parkinsonism associated with dementia and visual hallucinations fulfilling diagnostic criteria for Lewy Body Dementia (LBD) have been only rarely associated with PSEN1 and PSEN2 mutations [40, 58, 59]. "
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    • "Additional neurological symptoms and signs appear to occur more commonly in FAD than SAD; myoclonus and seizures have been reported in both APP and PSEN1 families [5] [13] [14] and PSEN1 mutations producing spastic paraparesis [15] and cerebellar ataxia [16] have also been described. Extrapyramidal signs have been reported in both PSEN1 [17] and PSEN2 subjects [18]. Although previous pathological studies have shown some differences between the sporadic and familial forms of the disease (reviewed in [19]), there are few studies directly comparing pathology in the different mutations. "
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